Human neutralizing antibodies against HIV env
Patent Information
- Authority / Receiving Office
- EP · EP
- Patent Type
- Applications
- Current Assignee / Owner
- INTERNATIONAL AIDS VACCINE INITIATIVE INC
- Filing Date
- 2024-08-29
- Publication Date
- 2026-07-08
AI Technical Summary
Current broadly neutralizing antibodies (bnAbs) against HIV-1 fail to neutralize all circulating HIV strains, limiting their effectiveness in preventing HIV infection.
Development of a monoclonal antibody or antigen-binding fragment that specifically binds to an HIV Env trimer, does not bind to the corresponding monomeric gp120 polypeptide, and competes with reference antibodies such as VRC01 or PC68-L31_54Q for binding to the HIV Env trimer.
The antibody achieves broad and potent neutralization of HIV strains, including those that are resistant to current bnAbs, by targeting conserved epitopes on the HIV Env trimer.
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Figure US2024044375_06032025_PF_FP_ABST
Abstract
Description
Human neutralizing antibodies against HIV Env GOVERNMENT INTEREST
[0001] The invention was made with government support under Cooperative Agreement No. AID- OAA-A-16-00032 awarded by the U.S. Agency for International Development (USAID) and under Grant No. UM1AI144462 awarded by the NIH / NIAID CHAVD. The U.S. government has certain rights in the invention. FIELD OF THE INVENTION
[0002] The field of the invention generally relates to anti-HIV Env antibodies and their use in the treatment or prevention of HIV / AIDS. CROSS-REFRENCE TO RELATED APPLICATIONS
[0003] This application claims the benefit of U.S. application no. 63 / 535,669, filed August 31, 2023, which is incorporated herein by reference in its entirety. REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY
[0004] The content of the electronically submitted sequence listing (Name: 6765_1401_Sequence Listing.xml, Size: 1,074,254 bytes, and Date of Creation: August 28, 2024) is herein incorporated by reference in its entirety. BACKGROUND
[0005] A successful HIV vaccine candidate should elicit broadly neutralizing antibodies (bnAbs) against the HIV envelope (Env) viral spike protein. Env is not particularly immunogenic due to shielding of conserved regions by N-linked glycans, and exposed epitopes vary widely in viral diversity. Burton et al., Nature Immunology 2015, 16 (6), 571. Therefore, HIV bnAbs that recognize vulnerable neutralizing epitopes on diverse Envs only naturally occur in a fraction of individuals, (Burton et al., Annu Rev Immunol 2016, 34, 635) but it has been demonstrated that sterilizing antibody responses play a key role in preventing viral acquisition in animal models. Peguet al., Immunological Reviews 2017, 275 (1), 296. Previously identified bnAbs predominantly target 7 main conserved neutralizing epitopes on Env termed, the CD4 (receptor) binding site (CD4bs), the V2 apex, N332 glycan site, gp120-gp41 interface, fusion peptide (FP), silent face, and the membrane proximal external region (MPER). Sok et al., Nature Immunology 2018, 19 (11), 1179. Soluble recombinant Env trimers with stabilized native-like conformations display neutralizing epitopes while occluding non-neutralizing epitopes, and are excellent tools to selectively isolate neutralizing antibodies from donors. Sanders et al., PLOS Pathogens 2013, 9 (9), e1003618; Binley et al., Journal of Virology 2000, 74 (2), 627; and Sanders et al., Immunological Reviews 2017, 275 (1), 161. Using such molecular tools, the repertoire of known bnAbs has expanded in the last decade , aiding in advancing HIV vaccine design as well as the development of HIV antibody therapeutics. van Gils et al., Virology 2013, 435 (1), 46; Steichen et al., Science 2019, 366 (6470); and Pegu et al., Immunological Reviews 2017, 275 (1), 296.
[0006] Because the CD4bs functions to mediate viral entry into host cells (Gallo et al., Biochimica et Biophysica Acta (BBA) - Biomembranes 2003, 1614 (1), 36), this region must be conserved and can only mutate at the cost of viral fitness (Dingens et al., Immunity 2019, 50 (2), 520). CD4bs directed bnAbs mimic and block the interaction between CD4 and the CD4bs (Wu et al., Science 2010, 329 (5993), 856) and tend to have broader coverage than bnAbs to other neutralizing epitopes (Sok et al., Nature Immunology 2018, 19 (11), 1179). However, CD4bs bnAbs tend to be highly mutated and take longer to develop within an individual, because antibodies of this class evolve to accommodate or avoid shielding glycans to increase neutralization breadth. Umotoy et al., Immunity 2019, 51 (1), 141; Crooks et al., PLOS Pathogens 2015, 11 (5), e1004932. Additionally, variable loops 1, 2 and 5 (V1, V2, V5) can restrict access to this epitope as well and rapid sequence alteration of these loops under immune pressure such as increasing N-linked glycosylation sites (PNGS), can lead to virus escape. Julien et al., Science 2013, 342 (6165), 1477; Doria-Rose et al., Journal of Virology 2012, 86 (15), 8319; LaBranche et al., PLOS Pathogens 2018, 14 (11), e1007431.
[0007] A key goal in HIV vaccine design is to elicit broadly neutralizing antibodies (bnAbs). Burton & Hangartner, Annu Rev Immunol 34, 635-659 (2016). Most bnAbs to HIV-1 have been cloned from elite donors whose plasma shows broad neutralizing activity. These bnAbs target 7 distinct sites on the HIV-1 envelope glycoprotein (Env) spike, including the CD4-binding site (CD4bs), V2 apex, N332 / V3 base supersite (also referred to as high-mannose patch epitope), silent face, gp120-gp41 interface, fusion peptide, and membrane-proximal external region (MPER). AsbnAbs arise from complex affinity maturation pathways, efforts are underway to dissect the structural and genetic bases of bnAb function to uncover common elements that can simplify vaccine design. Kwong & Mascola, Immunity 48, 855-871 (2018).
[0008] Given the absence of an effective vaccine for protection against HIV-1 infection, passive immunization strategies that utilize potent broadly neutralizing antibodies (bnAbs) to block acquisition of HIV-1 are being rigorously pursued in the clinical setting. Walsh & Seaman, Front Immunol.2021; 12: 712122. bnAbs have demonstrated robust protection in preclinical animal models, and several leading bnAb candidates have shown favorable safety and pharmacokinetic profiles when tested individually or in combinations in early phase human clinical trials. However, the currently available bnAbs fail to neutralize all circulating HIV strains.
[0009] Thus, there remains a need for the development of neutralizing antibodies that can be used in the treatment or prevention of HIV / AIDS. BRIEF SUMMARY
[0010] In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that binds to an HIV Env trimer, does not bind to the corresponding monomeric gp120 polypeptide of the HIV Env and competes with VRC01 for binding to the HIV Env trimer, optionally wherein the trimer is an SOSIP trimer, and optionally wherein the HIV Env is BG505 HIV Env.
[0011] In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof which binds to an HIV Env trimer, does not bind to the corresponding monomeric gp120 polypeptide of the HIV Env and competes with a reference antibody for binding to the HIV Env trimer, wherein the reference antibody is selected from the group consisting of the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K,PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68- L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H antibody, optionally wherein the trimer is an SOSIP trimer, and optionally wherein the HIV Env is BG505 HIV Env. In some embodiments, the reference antibody is the PC68-L31_54Q antibody.
[0012] In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof which binds to the same epitope of an HIV Env trimer as a reference antibody selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68- L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68- L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68- L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68- L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H antibody, optionally wherein the trimer is an SOSIP trimer, and optionally wherein the HIV Env is BG505 HIV Env. In some embodiments, the reference antibody is the PC68-L31_54Q antibody.
[0013] In some embodiments, the antibody or antigen-binding fragment thereof comprises (a) a VH and VL of the VH3-30 VL3-21 lineage, respectively; and (b) a VH CDR2 comprising a 5 amino acid insertion comprising the sequence of (V / I / L / P)(H / N / Q)(E / D)(Y / D / E / H)D (SEQ ID NO: 1261), wherein the insertion is between Kabat position 52 and 53. In some embodiments, the antibody or antigen-binding fragment thereof comprises (a) a VH CDR2 comprising the amino acid sequence of (D / H)(A / G / V / M)G(V / I / L / P)(H / N / Q)(E / D)(Y / D / E / H)D(V / T / I / L / A)(K / I / E)(H / Y / G / Q) (SEQ ID NO: 1262), (b) a VH CDR3 comprising the amino acid sequence of (A / G)KD(S / F / Y / L / I / V / R)(F / V / I / R)(A / T / P / G)(Y / F / L)(Y / W / H / R)(G / S / D / A)(Y / T)(N / S / K / R / G / H) GP(H / Y / E / D / Q)(S / V / I / T) (SEQ ID NO: 1263), and (c) a VL CDR3 comprising the amino acid sequence of (Y / H / Q / F)(M / I / V)W(D / H)G(S / R)(G / I / L / R)(V / A / P / S / L)(R / H / G) (SEQ ID NO: 1264).
[0014] In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein (a) the VH CDR1 comprises the VH CDR1 of an antibody described herein (e.g., PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68- L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68- L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68- L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68- L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I) comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions, (b) the VH CDR2 comprises the VH CDR2 of an antibody described herein comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions, (c) the VH CDR3 comprises the VH CDR3 of an antibody described herein comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions, (d) the VL CDR1 comprises the VL CDR1 of an antibody described herein comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions, (e) the VL CDR2 comprises the VL CDR2 of an antibody described herein comprising 0, 1, or 2 substitutions, insertions, or deletions, and / or (f) the VL CDR3 comprises the VL CDR3 of an antibody described herein comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the antibody comprises the PC68- L31_54Q VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3.
[0015] In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region (VH), wherein the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68- L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68- L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68- L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH and / or the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68- L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68- L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68- L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68- L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL. In some embodiments, the antibody comprises the PC68- L31_54Q VH and VL.
[0016] In one aspect, provided herein are pharmaceutical compositions comprising a monoclonal antibody or antigen-binding fragment thereof described herein or a polynucleotide (e.g., mRNA) encoding a monoclonal antibody or antigen-binding fragment thereof described herein.
[0017] In one aspect, provided herein are isolated polynucleotides (e.g., mRNA) encoding a monoclonal antibody or antigen-binding fragment thereof described herein.
[0018] In one aspect, provided herein are methods of producing a monoclonal antibody or antigen- binding fragment thereof described herein.
[0019] In one aspect, provided herein are methods of neutralizing an HIV virus, comprising contacting the virus with a monoclonal antibody or antigen-binding fragment thereof described herein.
[0020] In one aspect, provided herein are methods of reducing the likelihood of HIV infection in a subject exposed to HIV comprising administering to the subject a monoclonal antibody or antigen-binding fragment thereof described herein or a polynucleotide (e.g., mRNA) encoding a monoclonal antibody or antigen-binding fragment thereof described herein.
[0021] In one aspect, provided herein are methods of treating HIV / AIDS comprising administering to a subject in need thereof a monoclonal antibody or antigen-binding fragment thereof described herein or a polynucleotide (e.g., mRNA) encoding a monoclonal antibody or antigen-binding fragment thereof described herein.
[0022] In one aspect, provided herein are methods of reducing viral load comprising administering to a subject in need thereof a monoclonal antibody or antigen-binding fragment thereof described herein or a polynucleotide (e.g., mRNA) encoding a monoclonal antibody or antigen-binding fragment thereof described herein.
[0023] In one aspect, provided herein are methods of producing an engineered variant of a monoclonal antibody or antigen-binding fragment thereof described herein. BRIEF DESCRIPTION OF THE DRAWINGS
[0024] Figure 1. PC68 bnAb Lineage 31 characterization. Confirmation of neutralization breadth and potency.
[0025] Figure 2. PC68-L31 bnAb lineage (lineage #31) shows bnAb activity, high SHM and a defining CDRH2 insertion feature.
[0026] Figure 3. PC68-L31 targets an epitope that is distinct but overlaps with previously reported CD4bs bnAbs. Competition BLI of PC68 mAbs with other bnAbs of known epitopes. VRC01: CD4bs, PGT121: N332 glycan, PGT145: V2 apex, PGT151: gp120gp-41 interface.
[0027] Figure 4. PC68-L31 targets an epitope that is distinct but overlaps with previously reported CD4bs bnAbs.
[0028] Figure 5. PC68-L31 bnAbs neutralization breadth and potency are similar to VRC01 on Seaman Panel. Breadth as a function of neutralization potency on a large 118 pseudovirus panel shown.
[0029] Figure 6. PC68-L31 bnAbs do not depend on glycans. Fold change in neutralization following single point mutation. DETAILED DESCRIPTION
[0030] Provided herein is a lineage of highly broad and potent antibodies derived from Protocol C donor 68 that bind a quaternary CD4bs epitope that extends to the V3 region of the adjacent protomer. These antibodies are reminiscent of CD4bs antibodies with FWR3 insertions in combination with V3 specific antibodies and can bind both the conserved CD4bs region with their heavy chains and the conserved base of the V3 region on the adjacent protomer with their light chains. Although the CD4bs and V3 region tend to be heavily shielded by glycans, these antibodies completely avoid contact with the glycans that shield these regions. Because of their breath and potency, lineage 31 mAbs are suitable for use as prophylactics or therapeutics alone or in combination with other bnAbs. I. Definitions
[0031] To facilitate an understanding of the present invention, a number of terms and phrases are defined below.
[0032] The terms "human immunodeficiency virus" or "HIV," as used herein, refer generally to a retrovirus that is the causative agent for acquired immunodeficiency syndrome (AIDS), variants thereof (e.g., simian acquired immunodeficiency syndrome, SAIDS), and diseases, conditions, or opportunistic infections associated with AIDS or its variants, and includes HIV-Type 1 (HIV-1) and HIV-Type 2 (HIV-2) of any clade or strain therein, related retroviruses (e.g., simian immunodeficiency virus (SIV)), and variants thereof (e.g., engineered retroviruses, e.g., chimeric HIV viruses, e.g., simian-human immunodeficiency viruses (SHIVs)). In some embodiments, an HIV virus is an HIV-Type-1 virus. Previous names for HIV include human T-lymphotropic virus- III (HTLV-III), lymphadenopathy-associated virus (LAV), and AIDS-associated retrovirus (ARV).
[0033] As used herein, the term "clade" refers to related human immunodeficiency viruses (HIVs) classified according to their degree of genetic similarity. There are currently four known groups of HIV-1 isolates: M, N, O, and P. Group M (major strains) viruses are responsible for the majority of the global HIV epidemic. The other three groups, i.e., N, O and P are quite uncommon and only occur in Cameroon, Gabon and Equatorial Guinea. In some embodiments, an HIV virus is a GroupM HIV virus. Within group M, there are known to be at least nine genetically distinct subtypes or clades of HIV-1: subtypes or clades A, B, C, D, F, G, H, J and K. Additionally, different subtypes can combine genetic material to form a hybrid virus, known as a 'circulating recombinant form' (CRFs). Subtype / clade B is the dominant HIV subtype in the Americas, Western Europe and Australasia. Subtype / clade C is very common in the high AIDS prevalence countries of Southern Africa, as well as in the horn of Africa and India. Just under half of all people living with HIV have subtype C. In certain exemplary embodiments, methods described herein can be used to treat a subject (e.g., a human) infected with HIV (e.g., HIV-1) or to block or prevent HIV (e.g., HIV-1) infection in subject (e.g., a human) at risk of HIV transmission. The HIV may be of two, three, four, five, six, seven, eight, nine, ten, or more clades and / or two or more groups of HIV.
[0034] Acquired immune deficiency syndrome ("AIDS") is a disease caused by the human immunodeficiency virus, or HIV.
[0035] As used herein, the term "envelope glycoprotein" or "Env" refers to the glycoprotein that is expressed on the surface of the envelope of HIV virions and the surface of the plasma membrane of HIV infected cells. "Envelope glycoprotein" or "Env" encompass, but are not limited to, native Env, an isoform of Env, or a variant of Env (e.g., well-ordered trimer variant) derived from an HIV isolate, for example, BG505. In some embodiments, Env is a MD-39 variant Env (Steichen et al, 2016), repaired and stabilized (RnS) variant Env (Rutten et al, 2018), DS variant Env (Kwon et al, 2015), NFL-TD variant Env (Guenaga et al, 2016), or DS-BG505-chimera variant Env (Joyce et al, 2018). Env is the sole virally encoded gene product on the surface of the virus and, as such, is the only target of neutralizing antibodies. Env is a trimer of heterodimers composed of two non- covalently associated subunits: the receptor-binding gp120 and the gp41 containing the fusion machinery. Each subunit is derived from a gp160 precursor glycoprotein following cleavage by cellular furins. HIV-1 gp120 binds the CD4 molecule on the surface of human target T cells to initiate the viral entry process, and following co-receptor engagement, fusion is mediated by gp41. The gp41 domain comprises the fusion peptide, fusion peptide proximal region, heptad repeats 1 and 2 (HR1, HR2), the membrane proximal external region (MPER), the transmembrane domain (TM) and the cytoplasmic tail (CT). gp140 env is the uncleaved ectodomain of gp160.
[0036] The term "well-ordered Env trimer" or "well-ordered trimer" as used herein refers to an envelope glycoprotein trimer comprising three cleaved gp140 polypeptides that closely mimic the quaternary structure of the Env ectodomain on the surface of the envelope of HIV or SIV virions and the surface of the plasma membrane of HIV or SIV infected cells. In some embodiments, thegp120 and gp41 ectodomain is linked by a covalent linkage, for example, a disulfide bond. In some embodiments, the gp140 polypeptide comprises one or more mutations to promote trimer formation. In some embodiments, the gp140 polypeptide comprises one or more Cys substitutions to promote disulfide formation. In some embodiments, the well-ordered trimer is a SOSIP gp140 trimer. Well-ordered SOSIP trimers have been disclosed in US Patent Appl. Pub. No. 2014 / 0212458, and Sanders, R. W. et al., PLoS Pathog. 9, e1003618 (2013), each of which is incorporated by reference herein in its entirety. In some embodiments, the well-ordered trimer is a MD-39 trimer (Steichen et al, 2016), repaired and stabilized (RnS) trimer (Rutten et al, 2018), DS trimer (Kwon et al, 2015), NFL-TD trimer (Guenaga et al, 2016), or DS-BG505-chimera trimer (Joyce et al, 2018). In some embodiments, a well-ordered trimer is formed from a clade A Env. In some embodiments, a well-ordered trimer is formed from a clade B Env. In some embodiments, a well-ordered trimer is formed from a clade C Env. In some embodiments, a well-ordered trimer is formed from a circulating recombinant form Env, wherein 'circulating recombinant form' (CRF) refers to a hybrid virus comprising a combination of genetic material from different subtypes. In some embodiments, a well-ordered Env trimer is a native flexibly linked (NFL) trimer as described in Sharna, et al., Cell Reports, 11(4):539-50 (2015). In one embodiment, a well ordered trimer is BG505 SOSIP. In one embodiment, a well ordered trimer is BG505 SOSIP.664. In one embodiment, BG505 SOSIP.664 comprises the amino acid sequence of SEQ ID NO: 1270. In one embodiment, a nascent BG505 SOSIP.664 further comprises a leader sequence, wherein the nascent BG505 SOSIP.664 comprises the amino acid sequence of SEQ ID NO: 1271. In some embodiments, a well-ordered Env trimer is a DS-SOSIP as described in Chuang GY, et al., J. Virology, 91(10). pii: e02268-16 (2017). In some embodiments, a well-ordered trimer is formed from an SIV Env. In some embodiments, a well-ordered trimer is an SIV Env SOSIP. In some embodiments, the gp120 and gp41 ectodomain is linked by a peptide linker, for example, a Gly- Ser linker, as described in Georgiev IS, et al., J. Virology 89(10): 5318-5329 (2015). In some embodiments, the well-ordered Env trimer is stable.
[0037] The term "antibody" means an immunoglobulin molecule (or a group of immunoglobulin molecules) that recognizes and specifically binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or combinations of the foregoing through at least one antigen recognition site within the variable region of the immunoglobulin molecule. As used herein, the terms "antibody" and "antibodies" are terms of art and can be used interchangeably herein and refer to a molecule with an antigen-binding site that specifically binds an antigen.
[0038] Antibodies can include, for example, monoclonal antibodies, recombinantly produced antibodies, human antibodies, humanized antibodies, resurfaced antibodies, chimeric antibodies, immunoglobulins, synthetic antibodies, tetrameric antibodies comprising two heavy chain and two light chain molecules, an antibody light chain monomer, an antibody heavy chain monomer, an antibody light chain dimer, an antibody heavy chain dimer, an antibody light chain- antibody heavy chain pair, intrabodies, heteroconjugate antibodies, single domain antibodies, monovalent antibodies, single chain antibodies or single-chain Fvs (scFv), affybodies, Fab fragments, F(ab')2fragments, disulfide-linked Fvs (sdFv), anti-idiotypic (anti-Id) antibodies (including, e.g., anti-anti- Id antibodies), bispecific antibodies, and multi-specific antibodies. In certain embodiments, antibodies described herein refer to polyclonal antibody populations. Antibodies can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, or IgY), any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, or IgA2), or any subclasses (isotypes) thereof (e.g. IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2), of immunoglobulin molecule, based on the identity of their heavy-chain constant domains referred to as alpha, delta, epsilon, gamma, and mu, respectively. The different classes of immunoglobulins have different and well-known subunit structures and three-dimensional configurations. Antibodies can be naked or conjugated or fused to other molecules such as toxins, radioisotopes, other polypeptides etc.
[0039] As used herein, the terms "antigen-binding domain," "antigen-binding region," "antigen- binding site," and similar terms refer to the portion of antibody molecules, which comprises the amino acid residues that confer on the antibody molecule its specificity for the antigen (e.g., HIV Env). The antigen-binding region can be derived from any animal species, such as mouse and humans.
[0040] As used herein, the terms "variable region" or "variable domain" are used interchangeably and are common in the art. The variability in sequence is concentrated in those regions called complementarity determining regions (CDRs) while the more highly conserved regions in the variable domain are called framework regions (FR). Without wishing to be bound by any particular mechanism or theory, it is believed that the CDRs of the light and heavy chains are primarily responsible for the interaction and specificity of the antibody with antigen (e.g., HIV Env). In certain embodiments, the variable region comprises 3 CDRs (CDR1, CDR2, and CDR3) and 4 framework regions (FR1, FR2, FR3, and FR4) in the order of FR1-CDR1-FR2-CDR2-FR3-CDR3- FR4 from the N terminus to the C terminus. In certain embodiments, the variable region is a human variable region. In certain embodiments, the variable region comprises human CDRs and humanframework regions (FRs). In certain embodiments, the variable region comprises CDRs and framework regions (FRs) wherein one or more of the CDRs were modified by a substitution, deletion, or insertion relative to the CDRs of a parental antibody. In certain embodiments, the variable region comprises CDRs and framework regions (FRs) wherein one or more of the FRs were modified by a substitution, deletion, or insertion relative to the FRs of a parental antibody. In certain embodiments, the variable region comprises CDRs and framework regions (FRs) wherein one or more of the CDRs and one or more of the FRs were modified by a substitution, deletion, or insertion relative to the CDRs and FRs of a parental antibody. In certain embodiments, the variable region comprises human CDRs and primate (e.g., non-human primate) framework regions (FRs).
[0041] A skilled artisan understands that there are several methods for determining CDRs. One approach is based on cross-species sequence variability (i.e., Kabat EA, et al., Sequences of Proteins of Immunological Interest, (5th ed., 1991, National Institutes of Health, Bethesda Md.) ("Kabat"). Another approach is based on crystallographic studies of antigen-antibody complexes (Al-lazikani B., et al, J. Mol. Biol.273:927-948 (1997)) ("Chothia"). In addition, combinations of these two approaches are sometimes used in the art to determine CDRs. In some embodiments, the CDR sequences are identified according to Kabat. In some embodiments, the CDR sequences are identified according to Chothia. In some embodiments, the CDR sequences are identified according to IMGT. Lefrnac et al., Dev. Comp. Immunol., 27, 55-77 (2003). It is understood that the identification of CDRs in a variable region also identifies the FRs as the sequences flanking the CDRs.
[0042] The Kabat numbering system is generally used when referring to a residue in the variable domain (approximately residues 1-107 of the light chain and residues 1-113 of the heavy chain) (e.g., Kabat EA, et al., Sequences of Immunological Interest. (5th Ed., 1991, National Institutes of Health, Bethesda, Md.) ("Kabat").
[0043] The amino acid position numbering as in Kabat, refers to the numbering system used for heavy chain variable domains or light chain variable domains of the compilation of antibodies in Kabat EA, et al. (Sequences of Immunological Interest. (5th Ed., 1991, National Institutes of Health, Bethesda, Md.), "Kabat"). Using this numbering system, the actual linear amino acid sequence can contain fewer or additional amino acids corresponding to a shortening of, or insertion into, a FR or CDR of the variable domain. For example, a heavy chain variable domain can include a single amino acid insert (residue 52a according to Kabat) after residue 52 of H2 and inserted residues (e.g. residues 82a, 82b, and 82c, etc. according to Kabat) after heavy chain FR residue 82.The Kabat numbering of residues can be determined for a given antibody by alignment at regions of homology of the sequence of the antibody with a "standard" Kabat numbered sequence. Chothia refers instead to the location of the structural loops (Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). The end of the Chothia CDR-H1 loop when numbered using the Kabat numbering convention varies between H32 and H34 depending on the length of the loop (this is because the Kabat numbering scheme places the insertions at H35A and H35B; if neither 35A nor 35B is present, the loop ends at 32; if only 35A is present, the loop ends at 33; if both 35A and 35B are present, the loop ends at 34). The AbM hypervariable regions represent a compromise between the Kabat CDRs and Chothia structural loops, and are used by Oxford Molecular's AbM antibody modeling software, available, for example, at bioinf.org.uk / abs / software. In some embodiments, the CDR sequences are identified according to Kabat. In some embodiments, the CDR sequences are identified according to Chothia. In some embodiments, the CDR sequences are identified according to AbM. In some embodiments, the CDR sequences are identified according to IMGT. Lefrnac et al., Dev. Comp. Immunol., 27, 55-77 (2003). In some embodiments, the VH CDR3 sequence is identified according to Kabat. In some embodiments, the VH CDR3 sequence is identified according to Chothia. In some embodiments, the VH CDR3 sequence is identified according to AbM. In some embodiments, the VH CDR sequence is identified according to IMGT. Lefrnac et al., Dev. Comp. Immunol., 27, 55-77 (2003).
[0044] The terms "VL" and "VL domain" are used interchangeably to refer to the light chain variable region of an antibody.
[0045] The terms "VH" and "VH domain" are used interchangeably to refer to the heavy chain variable region of an antibody.
[0046] The term "antibody fragment" refers to a portion of an intact antibody. An "antigen-binding fragment" refers to a portion of an intact antibody that binds to an antigen. An antigen-binding fragment can contain the antigenic determining variable regions of an intact antibody. Examples of antibody fragments include, but are not limited to Fab, Fab', F(ab')2, and Fv fragments, linear antibodies, and single chain antibodies.
[0047] A "monoclonal" antibody or antigen-binding fragment thereof refers to a homogeneous antibody or antigen-binding fragment population involved in the highly specific recognition and binding of a single antigenic determinant, or epitope. This is in contrast to polyclonal antibodies that typically include different antibodies directed against different antigenic determinants. The term "monoclonal" antibody or antigen-binding fragment thereof encompasses both intact and full- length monoclonal antibodies as well as antibody fragments (such as Fab, Fab', F(ab')2, Fv), single chain (scFv) mutants, fusion proteins comprising an antibody portion, and any other modified immunoglobulin molecule comprising an antigen recognition site. Furthermore, "monoclonal" antibody or antigen-binding fragment thereof refers to such antibodies and antigen-binding fragments thereof made in any number of manners including but not limited to by hybridoma, phage selection, recombinant expression, and transgenic animals.
[0048] The term "polyclonal antibody" describes a composition of different (diverse) antibody molecules, which are capable of binding to or reacting with several different specific antigenic determinants on the same or on different antigens. Usually, the variability of a polyclonal antibody is primarily located in the so-called variable regions of the polyclonal antibody, in particular in the CDR regions. In the present disclosure, a mixture of two or more polyclonal antibodies (a polycomposition) is produced in one mixture from a polyclonal polycomposition cell line, which is produced from two or more parental polyclonal cell lines each expressing antibody molecules, which are capable of binding to a distinct target, but it may also be a mixture of two or more polyclonal antibodies produced separately. A mixture of monoclonal antibodies providing the same antigen / epitope coverage as a polyclonal antibody described herein will be considered as an equivalent of a polyclonal antibody.
[0049] The term "chimeric" antibodies or antigen-binding fragments thereof refers to antibodies or antigen-binding fragments thereof wherein the amino acid sequence is derived from two or more species. Typically, the variable region of both light and heavy chains corresponds to the variable region of antibodies or antigen-binding fragments thereof derived from one species of mammals (e.g., mouse) with the desired specificity, affinity, and capability, while the constant regions arehomologous to the sequences in antibodies or antigen-binding fragments thereof derived from another (usually human) to avoid eliciting an immune response in that species.
[0050] The term "epitope" or "antigenic determinant" are used interchangeably herein and refer to that portion of an antigen capable of being recognized and specifically bound by a particular antibody. When the antigen is a polypeptide, epitopes can be formed both from contiguous amino acids and noncontiguous amino acids juxtaposed by tertiary folding of a protein. Epitopes formed from contiguous amino acids are typically retained upon protein denaturing, whereas epitopes formed by tertiary folding are typically lost upon protein denaturing. An epitope typically includes at least 3, and more usually, at least 5 or 8-10 amino acids in a unique spatial conformation.
[0051] "Binding affinity" generally refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, "binding affinity" refers to intrinsic binding affinity, which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (KD). Affinity can be measured by common methods known in the art, including those described herein. Low-affinity antibodies generally bind antigen slowly and tend to dissociate readily, whereas high-affinity antibodies generally bind antigen faster and tend to remain bound longer. A variety of methods of measuring binding affinity are known in the art, any of which can be used for purposes of the present invention. Specific illustrative embodiments are described in the following. In certain embodiments, an anti-HIV antibody described herein binds to HIV Env trimer (e.g., BG505 SOSIP ) with a KDof at least about 0.1 ^M or less, at least about 0.01 ^M or less, at least about 1 nM or less, or at least about 0.1 nM or less. In certain embodiments, an anti-HIV antibody described herein binds to HIV Env trimer with a KDof at least about 0.01 ^M or less. In some embodiments, the HIV Env trimer is BG505 SOSIP. In some embodiments, an anti-HIV antibody described herein is capable of binding to cells that express functional, well- ordered HIV-1 membrane Env trimers. In some embodiments, an anti-HIV antibody described herein is capable of binding to HIV Env trimer in biolayer interferometry (BLI) assay. In some embodiments, an anti-HIV antibody described herein is capable of binding to HIV Env trimer in ELISA. In some embodiments, an anti-HIV antibody described herein is capable of binding Env trimers from detergent-solubilized HIV-1 virions in an ELISA assay. In one example, the antibody may specifically bind to Env trimers from detergent-solubilized HIV-1 virions in a BN-PAGE gel mobility-shift assay.
[0052] "Or better" when used herein to refer to binding affinity refers to a stronger binding between a molecule and its binding partner. "Or better" when used herein refers to a stronger binding, represented by a smaller numerical KDvalue. For example, an antibody, which has an affinity for an antigen of "0.6 nM or better", the antibody's affinity for the antigen is <0.6 nM, i.e. 0.59 nM, 0.58 nM, 0.57 nM etc. or any value less than 0.6 nM.
[0053] As used herein, the terms "immunospecifically binds," "immunospecifically recognizes," "specifically binds," and "specifically recognizes" are analogous terms in the context of antibodies and refer to molecules that bind to an antigen (e.g., epitope or immune complex) as such binding is understood by one skilled in the art. For example, a molecule that specifically binds to an antigen can bind to other peptides or polypeptides, generally with lower affinity as determined by, e.g., immunoassays, BIAcore®, KinExA 3000 instrument (Sapidyne Instruments, Boise, ID), ELISA, biolayer interferometry (BLI), flow cytometry or other assays known in the art. In a specific embodiment, molecules that immunospecifically bind to an antigen bind to the antigen with a KDthat is at least 2 logs, 2.5 logs, 3 logs, or 4 logs lower than the KDwhen the molecules bind non- specifically to another antigen. In one example, the antibody may specifically bind to cells that express functional, well-ordered HIV-1 membrane Env trimers. In one example, the antibody may specifically bind to the HIV Env trimer. In one example, the antibody may specifically bind to the HIV Env trimer (e.g., Bg505 SOSIP) in biolayer interferometry (BLI) assay. In one example, the antibody may specifically bind to the HIV Env trimer in ELISA assay. In one example, the antibody may specifically bind to Env trimers from detergent-solubilized HIV-1 virions. In one example, the antibody may specifically bind to Env trimers from detergent-solubilized HIV-1 virions in an ELISA assay. In one example, the antibody may specifically bind to Env trimers from detergent- solubilized HIV-1 virions in a BN-PAGE gel mobility-shift assay. The antibody may bind to HIV Env trimer with a KDat least 2 logs, 2.5 logs, 3 logs, or 4 logs lower than KDof binding to other viral or non-viral polypeptides. An antibody that specifically binds to Env trimer encompass, but are not limited to, antibodies that specifically bind to native Env, an isoform of Env, or a variant of Env derived from an HIV isolate.
[0054] By "preferentially binds," it is meant that the antibody specifically binds to an epitope more readily than it would bind to a related, similar, homologous, or analogous epitope. Thus, an antibody, which "preferentially binds" to a given epitope would more likely bind to that epitope than to a related epitope, even though such an antibody may cross-react with the related epitope.
[0055] An antibody is said to "competitively inhibit" binding of a reference antibody to a given epitope if it preferentially binds to that epitope or an overlapping epitope to the extent that it blocks, to some degree, binding of the reference antibody to the epitope. Competitive inhibition may be determined by any method known in the art, for example, competition ELISA assays. An antibody may be said to competitively inhibit binding of the reference antibody to a given epitope by at least 90%, at least 80%, at least 70%, at least 60%, or at least 50%.
[0056] The term "broadly neutralizing antibody" or "bnAb," as used herein, with respect to HIV (e.g., HIV-1), refers to an antibody that recognizes HIV Env of more than one isolate or strain of HIV and inhibits or prevents receptor binding of target cells as evaluated in an in vitro neutralization assay. In some embodiments, a broadly neutralizing antibody inhibits infection of a susceptible target cell by HIV. In some embodiments, a neutralizing (e.g., broadly neutralizing) antibody specifically binds an HIV Env and inhibits infection of a susceptible target cell (e.g., TZM-bl) by an HIV pseudovirus comprising an Env polypeptide. HIV pseudovirus neutralization assays have been disclosed in the art, for example, in Walker L.M., et al., Nature 477, 466–470 (2011), Li M., et al., J. Virol. 79:10108-10125 (2005), each of which is incorporated herein by reference in its entirety for all purposes. In some embodiments, a broadly neutralizing antibody neutralizes 2, 3, 4, 5, 6, 7, 8, 9, or more HIV strains or pseudoviruses. In some embodiments, a broadly neutralizing antibody neutralizes 2, 3, 4, 5, 6, 7, 8, 9, or more HIV strains or pseudoviruses that belong to the same or different clades. In some embodiments, a broadly neutralizing antibody is capable of neutralizing HIV strains or pseudoviruses from at least two different clades. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least one clade B strain or pseudovirus and one clade C strain or pseudovirus. In some embodiments, a broadly neutralizing antibody is capable of neutralizing more than one clade B strain or pseudovirus and more than one clade C strain or pseudovirus. In some embodiments, a broadly neutralizing antibody is capable of neutralizing an HIV strain or pseudovirus from at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten clades. In some embodiments, a broadly neutralizing antibody is capable of neutralizing an HIV strain or pseudovirus from at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least fifteen, or all sixteen clades selected from the group consisting of clades A, A (T / F), AC, ACD, B, B (T / F), BC, C, C (T / F), CD, CRF01_AE, CRF01_AE (T / F), CRF02_AG, D, D (T / F) and G. In some embodiments, a broadly neutralizing antibody is capableof neutralizing an HIV strain or pseudovirus from at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or all eleven clades selected from the group consisting of clades A, AC, ACD, AE, AG, B, BC, C, CD, D, D (T / F), and G.
[0057] In some embodiments, the breadth of neutralization is tested on an indicator virus panel comprising cross-clade HIV isolates. In some embodiments, the virus panel comprises the 13 cross- clade isolates listed in Figure 1. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least 2, 3, 4, 5, 6, 7, 8, 9 or 10 of the cross-clade HIV isolates in the 13-member indicator virus panel. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% of cross-clade HIV isolates in the 13-member indicator virus panel. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 40% of cross-clade HIV isolates in the 13-member indicator virus panel. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 50% of cross-clade HIV isolates in the 13-member indicator virus panel. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 60% of cross-clade HIV isolates in the 13-member indicator virus panel. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 70% of cross-clade HIV isolates in the 13-member indicator virus panel. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 80% of cross-clade HIV isolates in the 13-member indicator virus panel. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 90% of cross-clade HIV isolates in the 13-member indicator virus panel.
[0058] In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% of cross-clade HIV isolates in the 13- member indicator virus panel with a median IC50equal to or less than about 2 µg / ml, about 1.5 µg / ml, about 1 µg / ml, about 0.75 µg / ml, about 0.5 µg / ml, about 0.25 µg / ml, about 0.1 µg / ml, 0.07 µg / ml, 0.06 µg / ml, 0.05 µg / ml, 0.025 µg / ml, 0.01 µg / ml or 0.005 µg / ml. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 40% of cross-clade HIV isolates in the 13-member indicator virus panel with a median IC50equal to or less than 0.75 µg / ml. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 40% of cross-clade HIV isolates in the 13-member indicator virus panel with a median IC50equal to or less than 0.5 µg / ml. In some embodiments, a broadly neutralizing antibody is capable ofneutralizing at least about 40% of cross-clade HIV isolates in the 13-member indicator virus panel with a median IC50equal to or less than 0.25 µg / ml.
[0059] In some embodiments, the breadth of neutralization is tested on an indicator virus panel comprising cross-clade HIV isolates. In some embodiments, the virus panel comprises the 119 cross-clade isolates listed in Table 4. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 30%, 40%, 50%, 60%, 70%, 80%, or 90%, or 100% of cross- clade HIV isolates in the 119-member indicator virus panel. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 40% of cross-clade HIV isolates in the 119-member indicator virus panel. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 50% of cross-clade HIV isolates in the 119-member indicator virus panel. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 60% of cross-clade HIV isolates in the 119-member indicator virus panel. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 70% of cross- clade HIV isolates in the 119-member indicator virus panel. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 80% of cross-clade HIV isolates in the 119-member indicator virus panel. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 90% of cross-clade HIV isolates in the 119-member indicator virus panel.
[0060] In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% of cross-clade HIV isolates in the 119- member indicator virus panel with a median IC50equal to or less than about 2 µg / ml, about 1.5 µg / ml, about 1 µg / ml, about 0.75 µg / ml, about 0.5 µg / ml, about 0.25 µg / ml, about 0.1 µg / ml, 0.07 µg / ml, 0.06 µg / ml, 0.05 µg / ml, 0.025 µg / ml, 0.01 µg / ml or 0.005 µg / ml. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 60% of cross-clade HIV isolates in the 119-member indicator virus panel with a median IC50equal to or less than 0.1 µg / ml. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 60% of cross-clade HIV isolates in the 119-member indicator virus panel with a median IC50equal to or less than 0.75 µg / ml. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 60% of cross-clade HIV isolates in the 119-member indicator virus panel with a median IC50equal to or less than 0.5 µg / ml. In some embodiments, a broadly neutralizing antibody is capable of neutralizing at least about 60% of cross-clade HIV isolates in the 119- member indicator virus panel with a median IC50equal to or less than 0.25 µg / ml.
[0061] The term "IC50" refers to the half maximal inhibitory concentration of an inhibitor, e.g., a broadly neutralizing antibody. For example, IC50is the concentration of an inhibitor, e.g., a broadly neutralizing antibody, where the response, e.g., infection by pseudovirus, is reduced by half.
[0062] The term "IC80" refers to the concentration of an inhibitor, e.g., a broadly neutralizing antibody, where the response, e.g., infection by pseudovirus, is reduced by 80%.
[0063] The phrase "substantially similar," or "substantially the same", as used herein, denotes a sufficiently high degree of similarity between two numeric values (generally one associated with an antibody described herein and the other associated with a reference / comparator antibody) such that one of skill in the art would consider the difference between the two values to be of little or no biological and / or statistical significance within the context of the biological characteristic measured by said values (e.g., KDvalues). The difference between said two values can be less than about 50%, less than about 40%, less than about 30%, less than about 20%, or less than about 10% as a function of the value for the reference / comparator antibody.
[0064] A polypeptide, antibody, polynucleotide, vector, cell, or composition, which is "isolated" is a polypeptide, antibody, polynucleotide, vector, cell, or composition, which is in a form not found in nature. Isolated polypeptides, antibodies, polynucleotides, vectors, cell or compositions include those which have been purified to a degree that they are no longer in a form in which they are found in nature. In some embodiments, an antibody, polynucleotide, vector, cell, or composition, which is isolated is substantially pure.
[0065] As used herein, "substantially pure" refers to material, which is at least 50% pure (i.e., free from contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 99% pure.
[0066] The terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymer can be linear or branched, it can comprise modified amino acids, and it can be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art. It is understood that, because the polypeptides described herein are based upon antibodies, in certain embodiments, the polypeptides can occur as single chains or associated chains.
[0067] The terms "identical" or percent "identity" in the context of two or more nucleic acids or polypeptides, refer to two or more sequences or subsequences that are the same or have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned (introducing gaps, if necessary) for maximum correspondence, not considering any conservative amino acid substitutions as part of the sequence identity. The percent identity can be measured using sequence comparison software or algorithms or by visual inspection. Various algorithms and software are known in the art that can be used to obtain alignments of amino acid or nucleotide sequences. One such non-limiting example of a sequence alignment algorithm is the algorithm described in Karlin S., et al, Proc. Natl. Acad. Sci., 87:2264-2268 (1990), as modified in Karlin S., et al., Proc. Natl. Acad. Sci., 90:5873-5877 (1993), and incorporated into the NBLAST and XBLAST programs (Altschul SF, et al., Nucleic Acids Res., 25:3389-3402 (1991)). In certain embodiments, Gapped BLAST can be used as described in Altschul SF, et al., Nucleic Acids Res. 25:3389-3402 (1997). BLAST-2, WU-BLAST-2 (Altschul SF, et al., Methods in Enzymology, 266:460-480 (1996)), ALIGN, ALIGN-2 (Genentech, South San Francisco, California) or Megalign (DNASTAR) are additional publicly available software programs that can be used to align sequences. In certain embodiments, the percent identity between two nucleotide sequences is determined using the GAP program in GCG software (e.g., using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 90 and a length weight of 1, 2, 3, 4, 5, or 6). In certain alternative embodiments, the GAP program in the GCG software package, which incorporates the algorithm of Needleman and Wunsch (J. Mol. Biol. (48):444-453 (1970)) can be used to determine the percent identity between two amino acid sequences (e.g., using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5). Alternatively, in certain embodiments, the percent identity between nucleotide or amino acid sequences is determined using the algorithm of Myers and Miller (CABIOS, 4:11-17 (1989)). For example, the percent identity can be determined using the ALIGN program (version 2.0) and using a PAM120 with residue table, a gap length penalty of 12 and a gap penalty of 4. Appropriate parameters for maximal alignment by particular alignment software can be determined by one skilled in the art. In certain embodiments, the default parameters of the alignment software are used. In certain embodiments, the percentage identity "X" of a first amino acid sequence to a second sequence amino acid is calculated as 100 x (Y / Z), where Y is the number of amino acid residues scored as identical matches in the alignment of the first and second sequences (as aligned by visual inspection or a particular sequence alignment program) and Z is the total number of residues in thesecond sequence. If the length of a first sequence is longer than the second sequence, the percent identity of the first sequence to the second sequence will be higher than the percent identity of the second sequence to the first sequence.
[0068] As a non-limiting example, whether any particular polynucleotide has a certain percentage sequence identity (e.g., is at least 80% identical, at least 85% identical, at least 90% identical, and in some embodiments, at least 95%, 96%, 97%, 98%, or 99% identical) to a reference sequence can, in certain embodiments, be determined using the Bestfit program (Wisconsin Sequence Analysis Package, Version 8 for Unix, Genetics Computer Group, University Research Park, 575 Science Drive, Madison, WI 53711). Bestfit uses the local homology algorithm of Smith and Waterman (Advances in Applied Mathematics 2: 482 489 (1981)) to find the best segment of homology between two sequences. When using Bestfit or any other sequence alignment program to determine whether a particular sequence is, for instance, 95% identical to a reference sequence described herein, the parameters are set such that the percentage of identity is calculated over the full length of the reference nucleotide sequence and that gaps in identity of up to 5% of the total number of nucleotides in the reference sequence are allowed.
[0069] In some embodiments, two nucleic acids or polypeptides described herein are substantially identical, meaning they have at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, and in some embodiments at least 95%, 96%, 97%, 98%, 99% nucleotide or amino acid residue identity, when compared and aligned for maximum correspondence, as measured using a sequence comparison algorithm or by visual inspection. Identity can exist over a region of the sequences that is at least about 10, about 20, about 40-60 residues in length or any integral value there between, and can be over a longer region than 60-80 residues, for example, at least about 90-100 residues, and in some embodiments, the sequences are substantially identical over the full length of the sequences being compared, such as the coding region of a nucleotide sequence for example.
[0070] A "conservative amino acid substitution" is one in which one amino acid residue is replaced with another amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). For example, substitution of a phenylalanine for a tyrosine is a conservativesubstitution. In some embodiments, conservative substitutions in the sequences of the polypeptides and antibodies described herein do not abrogate the binding of the polypeptide or antibody containing the amino acid sequence, to the antigen(s). Methods of identifying nucleotide and amino acid conservative substitutions, which do not eliminate antigen binding are well-known in the art (see, e.g., Brummell DA, et al., Biochem. 32: 1180-1187 (1993); Kobayashi et al., Protein Eng. 12(10):879-884 (1999); and Burks EA, et al., Proc. Natl. Acad. Sci. USA 94:.412-417 (1997)).
[0071] As used herein, the terms "treatment" or "therapy" (as well as different forms thereof, including curative or palliative) refer to treatment of an infected person. As used herein, the term "treating" includes alleviating or reducing at least one adverse or negative effect or symptom of a condition, disease or disorder. This condition, disease or disorder can be HIV infection.
[0072] Terms such as "treating" or "treatment" or "to treat" or "alleviating" or "to alleviate" refer to therapeutic measures that cure, slow down, lessen symptoms of, and / or halt progression of a diagnosed pathologic condition or disorder, such as HIV or AIDS. Thus, those in need of treatment include those already diagnosed with or suspected of having the disorder. In certain embodiments, a subject is successfully "treated" for the disorder according to the methods described herein if the patient shows one or more of the following: a reduction in the number of or complete absence of viral load; a reduction in the viral burden; inhibition of or an absence of the virus into peripheral organs; relief of one or more symptoms associated with the disorder; reduced morbidity and mortality; improvement in quality of life; increased progression-free survival (PFS), disease-free survival (DFS), or overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), a decrease in progressive disease (PD), a reduced time to progression (TTP), or any combination thereof.
[0073] As used herein, the terms "prevention" or "prophylaxis" refer to preventing a subject from becoming infected with, or reducing the risk of a subject from becoming infected with, or halting transmission of, or the reducing the risk of transmission of a virus. Prophylactic or preventative measures refer to measures that prevent and / or slow the development of a targeted pathological condition or disorder. Thus, those in need of prophylactic or preventative measures include those prone to have the disorder and those in whom the disorder is to be prevented. In some embodiments, prevention encompasses passive immunization of a subject in need thereof comprising administering an effective amount of an antibody described herein.
[0074] As employed above and throughout the disclosure the term "effective amount" refers to an amount effective, at dosages, and for periods of time necessary, to achieve the desired result withrespect to the treatment of the relevant disorder, condition, or side effect. An "effective amount" can be determined empirically and in a routine manner, in relation to the stated purpose. It will be appreciated that the effective amount of components of the present invention will vary from patient to patient not only with the particular vaccine, component or composition selected, the route of administration, and the ability of the components to elicit a desired result in the individual, but also with factors such as the disease state or severity of the condition to be alleviated, hormone levels, age, sex, weight of the individual, the state of being of the patient, and the severity of the pathological condition being treated, concurrent medication or special diets then being followed by the particular patient, and other factors, which those skilled in the art will recognize, with the appropriate dosage being at the discretion of the attending physician. Dosage regimes may be adjusted to provide an improved therapeutic response. An effective amount is also one in which any toxic or detrimental effects of the components are outweighed by the therapeutically beneficial effects.
[0075] The term "therapeutically effective amount" refers to an amount of an antibody, recombinant virus, immunoconjugate, or other drug effective to "treat" a disease or disorder in a subject or mammal. To the extent an antibody can prevent growth and / or kill existing cells, it can be cytostatic and / or cytotoxic. A "prophylactically effective amount" refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically but not necessarily, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease, the prophylactically effective amount will be less than the therapeutically effective amount.
[0076] The terms "subject," "individual," and "patient" are used interchangeably herein, and refer to an animal, for example a human, to whom treatment, including prophylactic treatment, with the antibody or pharmaceutical composition according to the present disclosure, is provided. In some embodiments, the subject, individual, or patient has been infected with HIV. In some embodiments, the subject, individual, or patient suffers from AIDS. In some embodiments, the subject, individual, or patient has been exposed to HIV. In some embodiments, the subject, individual, or patient is at risk of being exposed to HIV.
[0077] Administration "in combination with" one or more further therapeutic agents includes simultaneous (concurrent) or consecutive administration in any order.
[0078] The terms "pharmaceutically composition," "pharmaceutical formulation," "pharmaceutically acceptable formulation," or "pharmaceutically acceptable composition" all of which are used interchangeably, refer to those compounds, materials, compositions, and / or dosageforms which are, within the scope of sound medical judgment, suitable for contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem complications commensurate with a reasonable benefit / risk ratio. "Pharmaceutically acceptable" or "pharmaceutical formulation" refers to a preparation, which is in such form as to permit the biological activity of the active ingredient to be effective, and which contains no additional components, which are unacceptably toxic to a subject to which the formulation would be administered. The formulation can be sterile.
[0079] The term "antiretroviral therapy" or "ART," as used herein, refers to any of the therapies used to manage progression of a retrovirus (e.g., HIV) infection in a subject (e.g., a human), including, for example, nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors, entry inhibitors, maturation inhibitors, cellular inhibitors, integrase strand transfer inhibitors, and multi-class combinations. Such drugs include, but are not limited to, lamivudine and zidovudine, emtricitabine (FTC), zidovudine (ZDV), azidothymidine (AZT), lamivudine (3TC), zalcitabine, dideoxycytidine (ddC), tenofovir disoproxil fumarate (TDF), didanosine (ddl), stavudine (d4T), abacavir sulfate (ABC), etravirine (ETR), delavirdine (DLV), efavirenz (EFV), nevirapine (NVP), amprenavir (APV), tipranavir (TPV), indinavir (IDV), saquinavir, saquinavir mesylate (SQV), lopinavir (LPV), ritonavir (RTV), fosamprenavir calcium (FOS-APV), ritonavir (RTV), darunavir (DRV), atazanavir sulfate (ATV), nelfinavir mesylate (NFV), enfuvirtide (T-20), maraviroc and raltegravir. ART drugs can also include antibodies that target HIV proteins or cellular proteins associated with disease progression. Also included are immune-based therapies, such as IL-2, IL-12, and alpha- epibromide. Each of these drugs can be administered alone or in combination with any other ART drug or any HIV-specific neutralizing antibody, such as a broadly neutralizing antibody, which is incorporated by reference herein in its entirety for all purposes.
[0080] The term "reservoir activator," as used herein, refers to an agent capable of activating a viral reservoir (e.g., an HIV reservoir). In some embodiments, a reservoir activator comprises a histone deacytelase (HDAC) inhibitor (e.g., romidepsin, vorinostat, and panobinostat), immunologic activator (e.g., cytokines and TLR agonists), or a dedicated small molecule drug.
[0081] The term "immunomodulator," as used herein, refers to an agent, such as an antibody or peptide, which is capable of increasing, inducing, or extending an immune response (e.g., a cell- mediated immune response and / or a humoral immune response) when administered to a subject (e.g., a human, e.g., a human infected with HIV or at risk of an HIV infection or transmission).Immunomodulators include, but are not limited to immune checkpoint inhibitors, for example, a PD-1, PD-L1, LAG-3, or TIGIT antagonist. In some embodiments, an immunomodulator used in the methods described herein comprises an anti-PD-1 antibody, anti-PD-L1 antibody, anti-LAG3 antibody, or an anti-TIGIT antibody. An immunomodulator can be administered in conjunction with (e.g., prior to, concurrently with, or subsequent to, or within the context of a treatment regimen that includes the administration of a broadly neutralizing antibody described herein.
[0082] The terms "VRC01," and "VRC01 antibody" are used interchangeably herein to refer to an antibody with the same binding specificity as the VRC01 antibody disclosed by Wu et al., Science, 329(5993):856–61 (2010). In some embodiments, the VRC01 antibody comprises the VH and VL of SEQ ID NO: 1272 and 1273, respectively.
[0083] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to "a cell" includes a combination of two or more cells, and the like.
[0084] The term "and / or" as used in a phrase such as "A and / or B" herein is intended to include both "A and B," "A or B," "A," and "B." Likewise, the term "and / or" as used in a phrase such as "A, B, and / or C" is intended to encompass each of the following embodiments: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).
[0085] The term "about" as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of up to ±20% from the specified value, as such variations are appropriate to perform the disclosed methods. Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.
[0086] Notwithstanding that the numerical ranges and parameters setting forth the broad scope described herein are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
[0087] It is understood that wherever embodiments are described herein with the language "comprising," otherwise analogous embodiments described in terms of "consisting of" and / or "consisting essentially of" are also provided. II. Anti-HIV antibodies
[0088] In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that binds to an HIV Env trimer, does not bind to the corresponding monomeric gp120 polypeptide of the HIV Env and competes with VRC01 for binding to the HIV Env trimer. In some embodiments, the trimer is an SOSIP trimer. In some embodiments, the HIV Env is BG505 HIV Env. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH and VL of the VH3-30 VL3-21 lineage, respectively. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR2 comprising a 5 amino acid insertion comprising the sequence of (V / I / L / P)(H / N / Q)(E / D)(Y / D / E)D (SEQ ID NO: 1261), wherein the insertion is between Kabat position 52 and 53. In some embodiments, the antibody or antigen- binding fragment thereof comprises (a) a VH and VL of the VH3-30 VL3-21 lineage, respectively, and (b) a VH CDR2 comprising a 5 amino acid insertion comprising the sequence of (V / I / L / P)(H / N / Q)(E / D)(Y / D / E)D (SEQ ID NO: 1261), wherein the insertion is between Kabat position 52 and 53. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR2 comprising the amino acid sequence of (D / H)(A / G / V / M)G(V / I / L / P)(H / N / Q)(E / D)(Y / D / E / H)D(V / T / I / L / A)(K / I / E)(H / Y / G / Q) (SEQ ID NO: 1262). In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR3 comprising the amino acid sequence of (A / G)KD(S / F / Y / L / I / V / R)(F / V / I / R)(A / T / P / G)(Y / F / L)(Y / W / H / R)(G / S / D / A)(Y / T)(N / S / K / R / G / H) GP(H / Y / E / D / Q)(S / V / I / T) (SEQ ID NO: 1263). In some embodiments, the antibody or antigen- binding fragment thereof comprises a VL CDR3 comprising the amino acid sequence of (Y / H / Q / F)(M / I / V)W(D / H)G(S / R)(G / I / L / R)(V / A / P / S / L)(R / H / G) (SEQ ID NO: 1264). In some embodiments, the antibody or antigen-binding fragment thereof comprises (a) a VH CDR2 comprising the amino acid sequence of (D / H)(A / G / V / M)G(V / I / L / P)(H / N / Q)(E / D)(Y / D / E / H)D(V / T / I / L / A)(K / I / E)(H / Y / G / Q) (SEQ ID NO: 1262); (b) a VH CDR3 comprising the amino acid sequence of (A / G)KD(S / F / Y / L / I / V / R)(F / V / I / R)(A / T / P / G)(Y / F / L)(Y / W / H / R)(G / S / D / A)(Y / T)(N / S / K / R / G / H)GP(H / Y / E / D / Q)(S / V / I / T) (SEQ ID NO: 1263); and (c) a VL CDR3 comprising the amino acid sequence of (Y / H / Q / F)(M / I / V)W(D / H)G(S / R)(G / I / L / R)(V / A / P / S / L)(R / H / G) (SEQ ID NO: 1264).
[0089] In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof which binds to an HIV Env trimer, does not bind to the corresponding monomeric gp120 polypeptide of the HIV Env and competes with a reference antibody for binding to the HIV Env trimer, wherein the reference antibody is selected from the group consisting of the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68- L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H antibody. In some embodiments, the trimer is an SOSIP trimer. In some embodiments, the HIV Env is BG505 HIV Env. In some embodiments, the HIV Env is BG505 HIV Env. In some embodiments, the reference antibody is PC68-L31_54Q, i.e., a monoclonal antibody comprising the PC68-L31_54Q VH and VL. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH and VL of the VH3-30 VL3-21 lineage, respectively. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR2 comprising a 5 amino acid insertion comprising the sequence of (V / I / L / P)(H / N / Q)(E / D)(Y / D / E)D (SEQ ID NO: 1261), wherein the insertion is between Kabat position 52 and 53. In some embodiments, the antibody or antigen-binding fragment thereof comprises (a) a VH and VL of the VH3-30 VL3-21 lineage, respectively, and (b) a VH CDR2 comprising a 5 amino acid insertion comprising the sequence of (V / I / L / P)(H / N / Q)(E / D)(Y / D / E)D (SEQ ID NO: 1261), wherein the insertion is between Kabat position 52 and 53. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR2 comprising the amino acid sequence of (D / H)(A / G / V / M)G(V / I / L / P)(H / N / Q)(E / D)(Y / D / E / H)D(V / T / I / L / A)(K / I / E)(H / Y / G / Q) (SEQ IDNO: 1262). In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR3 comprising the amino acid sequence of (A / G)KD(S / F / Y / L / I / V / R)(F / V / I / R)(A / T / P / G)(Y / F / L)(Y / W / H / R)(G / S / D / A)(Y / T)(N / S / K / R / G / H) GP(H / Y / E / D / Q)(S / V / I / T) (SEQ ID NO: 1263). In some embodiments, the antibody or antigen- binding fragment thereof comprises a VL CDR3 comprising the amino acid sequence of (Y / H / Q / F)(M / I / V)W(D / H)G(S / R)(G / I / L / R)(V / A / P / S / L)(R / H / G) (SEQ ID NO: 1264). In some embodiments, the antibody or antigen-binding fragment thereof comprises (a) a VH CDR2 comprising the amino acid sequence of (D / H)(A / G / V / M)G(V / I / L / P)(H / N / Q)(E / D)(Y / D / E / H)D(V / T / I / L / A)(K / I / E)(H / Y / G / Q) (SEQ ID NO: 1262); (b) a VH CDR3 comprising the amino acid sequence of (A / G)KD(S / F / Y / L / I / V / R)(F / V / I / R)(A / T / P / G)(Y / F / L)(Y / W / H / R)(G / S / D / A)(Y / T)(N / S / K / R / G / H) GP(H / Y / E / D / Q)(S / V / I / T) (SEQ ID NO: 1263); and (c) a VL CDR3 comprising the amino acid sequence of (Y / H / Q / F)(M / I / V)W(D / H)G(S / R)(G / I / L / R)(V / A / P / S / L)(R / H / G) (SEQ ID NO: 1264).
[0090] In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof which binds to the same epitope of an HIV Env trimer as a reference antibody selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68- L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68- L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68- L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68- L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H antibody. In some embodiments, the trimer is an SOSIP trimer. In some embodiments, the HIV Env is BG505 HIV Env. In some embodiments, the HIV Env is BG505 HIV Env. In some embodiments, the reference antibody is PC68-L31_54Q, i.e., a monoclonal antibody comprising the PC68-L31_54Q VH and VL. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH and VL of the VH3-30 VL3-21 lineage, respectively. In someembodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR2 comprising a 5 amino acid insertion comprising the sequence of (V / I / L / P)(H / N / Q)(E / D)(Y / D / E)D (SEQ ID NO: 1261), wherein the insertion is between Kabat position 52 and 53. In some embodiments, the antibody or antigen-binding fragment thereof comprises (a) a VH and VL of the VH3-30 VL3-21 lineage, respectively, and (b) a VH CDR2 comprising a 5 amino acid insertion comprising the sequence of (V / I / L / P)(H / N / Q)(E / D)(Y / D / E)D (SEQ ID NO: 1261), wherein the insertion is between Kabat position 52 and 53. In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR2 comprising the amino acid sequence of (D / H)(A / G / V / M)G(V / I / L / P)(H / N / Q)(E / D)(Y / D / E / H)D(V / T / I / L / A)(K / I / E)(H / Y / G / Q) (SEQ ID NO: 1262). In some embodiments, the antibody or antigen-binding fragment thereof comprises a VH CDR3 comprising the amino acid sequence of (A / G)KD(S / F / Y / L / I / V / R)(F / V / I / R)(A / T / P / G)(Y / F / L)(Y / W / H / R)(G / S / D / A)(Y / T)(N / S / K / R / G / H) GP(H / Y / E / D / Q)(S / V / I / T) (SEQ ID NO: 1263). In some embodiments, the antibody or antigen- binding fragment thereof comprises a VL CDR3 comprising the amino acid sequence of (Y / H / Q / F)(M / I / V)W(D / H)G(S / R)(G / I / L / R)(V / A / P / S / L)(R / H / G) (SEQ ID NO: 1264). In some embodiments, the antibody or antigen-binding fragment thereof comprises (a) a VH CDR2 comprising the amino acid sequence of (D / H)(A / G / V / M)G(V / I / L / P)(H / N / Q)(E / D)(Y / D / E / H)D(V / T / I / L / A)(K / I / E)(H / Y / G / Q) (SEQ ID NO: 1262); (b) a VH CDR3 comprising the amino acid sequence of (A / G)KD(S / F / Y / L / I / V / R)(F / V / I / R)(A / T / P / G)(Y / F / L)(Y / W / H / R)(G / S / D / A)(Y / T)(N / S / K / R / G / H) GP(H / Y / E / D / Q)(S / V / I / T) (SEQ ID NO: 1263); and (c) a VL CDR3 comprising the amino acid sequence of (Y / H / Q / F)(M / I / V)W(D / H)G(S / R)(G / I / L / R)(V / A / P / S / L)(R / H / G) (SEQ ID NO: 1264).
[0091] In some embodiments, an antibody or antibody fragment described herein comprises one, two, three, four, five or six of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences shown in Table 1. In some embodiments, an antibody or antibody fragment described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequence shown in Table 1. Table 1. Example VH and VL CDR sequences. VH VH VH VL VL VL 3PC68-L31_32C 3 73 143 213 283 353 PC68-L31_32D 4 74 144 214 284 354PC68-L31_54C 42 112 182 252 322 392 PC68-L31_54D 43 113 183 253 323 393 Table 2. Variable heavy chain (VH) and light chain (VL) domains. VH VH AA VL AA nucl VL nuclPC68-L31_32K 431 501 571 641 PC68-L31_38A 432 502 572 642PC68-L31_54K 470 540 610 680 PC68-L31_54L 471 541 611 681 Table 3. Exampq . VH VH VH VH VL VL VL VL FW1 FW2 FW3 FW4 FW1 FW2 FW3 FW4 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8PC68-L31_43C 719 789 859 929 999 1069 1139 1209 PC68-L31_43D 720 790 860 930 1000 1070 1140 1210 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7PC68-L31_59A 758 828 898 968 1038 1108 1178 1248 PC68-L31_59B 759 829 899 969 1039 1109 1179 1249 0 1 2 3 4 5 6 [one, two, three, four, five or six of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences of a VH or VL shown in Table 2. In some embodiments, an antibody or antibody fragment described herein comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences of a VH or VL shown in Table 2. In some embodiments, an antibody or antibody fragment described herein comprises the VH CDR1, VH CDR2 and VH CDR3 of a single VH shown in Table 2. and a VL CDR1, VL CDR2, and VL CDR3 of a single VL shown in Table 2. In some embodiments, an antibody or antibody fragment described herein comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a single VH and its corresponding VL shown in Table 2. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 is according to Kabat. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 is as shown in Table 1.
[0093] In some embodiments, an antibody or antibody fragment described herein comprises a VH and VL having at least about 80% sequence identity, at least about 85% sequence identity, at least about 90% sequence identity, at least about 95% sequence identity, at least about 96% sequence identity, at least about 97% sequence identity, at least about 98% sequence identity, or at least about 99% sequence identity to a VH, a VL, or a VH and corresponding VL as shown in Table 2.
[0094] In some embodiments, an antibody or antibody fragment described herein comprises a VH, a VL, or a VH and corresponding VL as shown in Table 2.
[0095] In some embodiments, the antibody or antigen-binding fragment described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68- L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D,PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68- L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68- L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68- L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68- L31_59H VH CDR3 comprising 0, 1, 2, 3, 4 or 5 substitutions, insertions, or deletions.
[0096] In some embodiments, the antibody or antigen-binding fragment described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68- L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68- L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68- L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68- L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68- L31_59H VH CDR3 comprising 0, 1, 2, 3, 4 or 5 substitutions. In some embodiments, the VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR3. In some embodiments, the VH CDR3 comprises the PC68-L31_54Q VH CDR3 comprising 0, 1, 2, 3, 4 or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the PC68-L31_54Q VH CDR3 comprising 0, 1, 2, 3, 4 or 5 substitutions. In some embodiments, the VH CDR3 comprises the PC68-L31_54Q VH CDR3. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 is according to Kabat. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 is according to Table 1.
[0097] In some embodiments, the antibody or antigen-binding fragment described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, wherein the VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68- L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68- L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68- L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68- L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68- L31_59I VL CDR3 comprising 0, 1, 2, 3, 4 or 5 substitutions. In some embodiments, the VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR3. In some embodiments, the VL CDR3 comprises the PC68-L31_54Q VL CDR3 comprising 0, 1, 2, 3, 4 or 5 substitutions. In some embodiments, the VL CDR3 comprises the PC68-L31_54Q VL CDR3. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 is according to Kabat. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 is according to Table 1.
[0098] In some embodiments, the antibody or antigen-binding fragment described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 selected independently from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, PC68-L31_59H, and PC68-L31_59I VH CDR1s, VH CDR2s, VH CDR3s, VL CDR1s, VL CDR2s, and VL CDR3s. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises (i) the VH CDR1, VH CDR2, and VH CDR3 of a VH selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, and PC68-L31_59H VHs and (ii) a VL CDR1, VL CDR2, and VL CDR3 of a VL selected from the group consisting of the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68- L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, and PC68-L31_59I VLs. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a VH / VL pair selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68- L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68- L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P,PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68- L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68- L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H VH / VL pairs. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_43J VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 is according to Kabat. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 is according to Table 1.
[0099] In some embodiments, the antibody or antigen-binding fragment described herein comprises a VH and a VL, wherein (a) the VH comprises an amino acid sequence having at least about 90%, 95%, 97%, 98%, 99% or 100% identity to a VH selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, and PC68-L31_59H VHs and (b) the VL comprises an amino acid sequence having at least about 90%, 95%, 97%, 98%, 99% or 100% identity to a VL selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68- L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68- L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68- L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68- L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68- L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, and PC68-L31_59I VLs. In some embodiments, the VH and VL comprises a VH / VL pair selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68- L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68- L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68- L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68- L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68- L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H VH / VL pairs.
[0100] In some embodiments, the antibody or antigen-binding fragment described herein comprises a VH and a VL, wherein (i) the VH comprises an amino acid sequence having at least about 90%, 95%, 97%, 98%, 99% or 100% identity to the PC68-L31_54Q VH, and (ii) the VL comprises an amino acid sequence having at least about 90%, 95%, 97%, 98%, 99% or 100% identity to the PC68-L31_54Q VL. In some embodiments, the antibody or antigen-binding fragment described herein comprises a VH and a VL comprising an amino acid sequence having at least about 90%, 95%, 97%, 98%, 99% or 100% identity to the PC68-L31_54Q VH and VL, respectively. In some embodiments, the antibody or antigen-binding fragment described herein comprises the PC68-L31_54Q VH and VL, respectively.
[0101] In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR3 sequence shown in Table 1. In some embodiments, an isolated monoclonal antibody described herein comprises one, two, three, four, five or six of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences shown in Table 1. In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequence shown in Table 1. In some embodiments, an isolated monoclonal antibody described herein comprises a VH CDR3 sequence of a VH shown in Table 2. In some embodiments, an isolated monoclonal antibody described herein comprises one, two, three, four, five or six of the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences of a VH and VL shown in Table 2. In some embodiments, an isolated monoclonal antibody described herein comprises the VH CDR1, VH CDR2, and VH CDR3 sequences of a VH shown in Table 2 and the VL CDR1, VL CDR2, and VL CDR3 sequences of a VL shown in Table 2. In some embodiments, an isolated monoclonal antibody described herein comprises the VH CDR1, VH CDR2, and VH CDR3 sequences of a VH shown in Table 2 and the VL CDR1, VL CDR2, and VL CDR3 sequences of the corresponding VL shown in Table 2. In some embodiments, the CDR sequences are according to Kabat. In some embodiments, an isolated monoclonal antibody described herein comprises a VH, a VL, or a VH and VL as shown in Table 2. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding a HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR3 comprises the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions. In some embodiments, the VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR3. In some embodiments, the VH CDR3 comprises the PC68-L31_54Q VH CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, the VH CDR3 comprises the PC68-L31_54Q VH CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions. In some embodiments, the VH CDR3 comprises the PC68-L31_54Q VH CDR3. In some embodiments, the VH CDR3 isaccording to Kabat. In some embodiments, the VH CDR3 is according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect , provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding a HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein (a) the VH CDR1 comprises the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68- L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR1 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VH CDR2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68- L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68- L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68- L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68- L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68- L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR2 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and (c) the VH CDR3 comprises the PC68-L31_32A,PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68- L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68- L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68- L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68- L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68- L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, (a) the VH CDR1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR1 comprising 0, 1, 2, 3, 4, or 5 substitutions; (b) the VH CDR2 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR2 comprising 0, 1, 2, 3, 4, or 5 substitutions; and (c) the VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68- L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68- L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68- L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68- L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68- L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions. In some embodiments, (a) the VH CDR1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68- L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68- L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68- L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68- L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH CDR1; (b) the VH CDR2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR2; and (c) the VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR3. In some embodiments, (a) the VH CDR1 comprises the PC68-L31_54Q VH CDR1 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VH CDR2 comprises the PC68-L31_54Q VH CDR2 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and / or (c) the VH CDR3 comprises the PC68-L31_54Q VH CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, (a) the VH CDR1 comprises the PC68-L31_54Q VH CDR1 comprising 0, 1, 2, 3, 4, or 5 substitutions; (b) the VH CDR2 comprises the PC68- L31_54Q VH CDR2 comprising 0, 1, 2, 3, 4, or 5 substitutions; and / or (c) the VH CDR3 comprises the PC68-L31_54Q VH CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions. In some embodiments,(a) the VH CDR1 comprises the PC68-L31_54Q VH CDR1; (b) the VH CDR2 comprises the PC68-L31_54Q VH CDR2; and / or (c) the VH CDR3 comprises the PC68-L31_54Q VH CDR3. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68- L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68- L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68- L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68- L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68- L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR1, VH CDR2, and VH CDR3 independently comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions, respectively. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR1, VH CDR2, and VH CDR3 independently comprising 0, 1, 2, 3, 4, or 5 substitutions, respectively. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68- L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68- L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68- L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68- L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR1, VH CDR2, and VH CDR3, respectively. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, and VH CDR3 independently comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions, respectively. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, and VH CDR3 independently comprising 0, 1, 2, 3, 4, or 5 substitutions, respectively. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, and VH CDR3, respectively. In some embodiments, the VH CDR1, VH CDR2, and / or VH CDR3 is according to Kabat. In some embodiments, the VH CDR1, VH CDR2, and / or VH CDR3 is according to Table 1. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 is according to Kabat. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 is according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In some embodiments of the isolated monoclonal antibody or antigen-binding fragment thereof described herein, (a) the VL CDR1 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR1 comprising 0, 1, 2, 3, 4 or 5 substitutions, insertions, or deletions; (b) the VL CDR2 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR2 comprising 0, 1, 2, 3, 4 or 5 substitutions, insertions, or deletions; and (c) the VL CDR3 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR3 comprising 0, 1, 2, 3, 4 or 5 substitutions, insertions, or deletions. In some embodiments, (a) the VL CDR1 comprises the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F,PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68- L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR1 comprising 0, 1, 2, 3, 4 or 5 substitutions; (b) the VL CDR2 comprises the PC68-L31_32A, PC68-L31_32B, PC68- L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68- L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68- L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68- L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68- L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR2 comprising 0, 1, 2, 3, 4 or 5 substitutions; and (c) the VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68- L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68- L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68- L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68- L31_59I VL CDR3 comprising 0, 1, 2, 3, 4 or 5 substitutions. In some embodiments, (a) the VL CDR1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR1; (b) the VL CDR2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68- L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68- L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68- L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68- L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL CDR2; and (c) the VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68- L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A,PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68- L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68- L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68- L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68- L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR3. In some embodiments, (a) the VL CDR1 comprises the PC68-L31_54Q VL CDR1 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VL CDR2 comprises the PC68-L31_54Q VL CDR2 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and / or (c) the VL CDR3 comprises the PC68-L31_54Q VL CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, (a) the VL CDR1 comprises the PC68-L31_54Q VL CDR1 comprising 0, 1, 2, 3, 4, or 5 substitutions; (b) the VL CDR2 comprises the PC68-L31_54Q VL CDR2 comprising 0, 1, 2, 3, 4, or 5 substitutions; and / or (c) the VL CDR3 comprises the PC68- L31_54Q VL CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions. In some embodiments, (a) the VL CDR1 comprises the PC68-L31_54Q VL CDR1; (b) the VL CDR2 comprises the PC68-L31_54Q VL CDR2; and / or (c) the VL CDR3 comprises the PC68-L31_54Q VL CDR3. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E,PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR1, VL CDR2 and VL CDR3 independently comprising 0, 1, 2, 3, 4 or 5 substitutions, insertions, or deletions, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR1, VL CDR2 and VL CDR3 independently comprising 0, 1, 2, 3, 4 or 5 substitutions, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68- L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68- L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68- L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68- L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68- L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR1, VL CDR2 and VL CDR3, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the PC68-L31_54Q VL CDR1, VL CDR2 and VL CDR3 independently comprising 0, 1, 2, 3, 4 or 5 substitutions, insertions, or deletions, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprisesthe PC68-L31_54Q VL CDR1, VL CDR2 and VL CDR3 independently comprising 0, 1, 2, 3, 4 or 5 substitutions, respectively. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 comprises the PC68-L31_54Q VL CDR1, VL CDR2 and VL CDR3, respectively. In some embodiments, the VL CDR1, VL CDR2, and / or VL CDR3 is according to Kabat. In some embodiments, the VL CDR1, VL CDR2, and / or VL CDR3 is according to Table 1. In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 is according to Kabat. In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 is according to Table 1. In some embodiments of the isolated monoclonal antibody or antigen-binding fragment thereof described herein, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68- L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68- L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68- L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68- L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, or PC68-L31_59H VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 independently comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, or PC68-L31_59H VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 independently comprising 0, 1, 2, 3, 4, or 5 substitutions, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, or PC68-L31_59H VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68- L31_54Q VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 independently comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 independently comprising 0, 1, 2, 3, 4, or 5 substitutions, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 is according to Kabat. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 is according to Table 1. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 is according to Kabat.In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 is according to Table 1. In some embodiments of the isolated monoclonal antibody or antigen-binding fragment thereof described herein, the VH comprises a VH FW1, VH FW2, VH FW3 and VH FW4 and the VL comprises a VL FW1, VL FW2, VL FW3 and VL FW4, and wherein (a) the VH FW1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH FW1 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VH FW2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH FW2 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (c) the VH FW3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH FW3 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and (d) the VH FW4 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH FW4 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, (a) the VH FW1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68- L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68- L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68- L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C,PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68- L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68- L31_59H VH FW1 comprising 0, 1, 2, 3, 4, or 5 substitutions; (b) the VH FW2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH FW2 comprising 0, 1, 2, 3, 4, or 5 substitutions; (c) the VH FW3 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH FW3 comprising 0, 1, 2, 3, 4, or 5 substitutions; and (d) the VH FW4 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68- L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68- L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68- L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68- L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH FW4 comprising 0, 1, 2, 3, 4, or 5 substitutions. In some embodiments, (a) the VH FW1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68- L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68- L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68- L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68- L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH FW1; (b) the VH FW2 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A,PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH FW2; (c) the VH FW3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH FW3; and (d) the VH FW4 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68- L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68- L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68- L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68- L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68- L31_59H VH FW4. In some embodiments, the VH FW1, VH FW2, VH FW3 and VH FW4 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J,PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH FW1, VH FW2, VH FW3 and VH FW4, respectively. In some embodiments, the VH FW1, VH FW2, VH FW3 and VH FW4 comprises the PC68-L31_54Q VH FW1, VH FW2, VH FW3 and VH FW4. In some embodiments, VH FW1, VH FW2, VH FW3 and / or VH FW4 are according to Table 2. In some embodiments, VH FW1, VH FW2, VH FW3 and VH FW4 are according to Table 2. In some embodiments, (a) the VL FW1 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL FW1 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (b) the VL FW2 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B,PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL FW2 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; (c) the VL FW3 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL FW3 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions; and (d) the VL FW4 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L,PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL FW4 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions. In some embodiments, (a) the VL FW1 comprises the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68- L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL FW1 comprising 0, 1, 2, 3, 4, or 5 substitutions; (b) the VL FW2 comprises the PC68-L31_32A, PC68-L31_32B, PC68- L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68- L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68- L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68- L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68- L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL FW2 comprising 0, 1, 2, 3, 4, or 5 substitutions; (c) the VL FW3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL FW3 comprising 0, 1, 2, 3, 4, or 5 substitutions; and (d) the VL FW4 comprises the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68- L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL FW4 comprising 0, 1, 2, 3, 4, or 5 substitutions. In some embodiments, (a) the VL FW1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68- L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68- L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68- L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68- L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I; (b) the VL FW2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL FW2; (c) the VL FW3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL FW3; and (d) the VL FW4 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68- L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I,PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68- L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68- L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68- L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL FW4. In some embodiments, the VL FW1, VL FW2, VL FW3 and VL FW4 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68- L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68- L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68- L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68- L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68- L31_59I VL FW1, VL FW2, VL FW3 and VL FW4, respectively. In some embodiments, the VL FW1, VL FW2, VL FW3 and VL FW4 comprises the PC68-L31_54Q VL FW1, VL FW2, VL FW3 and VL FW4 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions, or deletions, respectively. In some embodiments, the VL FW1, VL FW2, VL FW3 and VL FW4 comprises the PC68- L31_54Q VL FW1, VL FW2, VL FW3 and VL FW4 comprising 0, 1, 2, 3, 4, or 5 substitutions, respectively. In some embodiments, the VL FW1, VL FW2, VL FW3 and VL FW4 comprises the PC68-L31_54Q VL FW1, VL FW2, VL FW3 and VL FW4, respectively. In some embodiments, the VL FW1, VL FW2, VL FW3 and / or VL FW4 are according to Table 2. In some embodiments, the VL FW1, VL FW2, VL FW3 and VL FW4 are according to Table 2. In some embodiments of the isolated monoclonal antibody or antigen-binding fragment thereof described herein, the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68- L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68- L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68- L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68- L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH. In some embodiments, the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68- L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68- L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68- L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68- L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68- L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL. In some embodiments, the VH and VL comprise the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, or PC68-L31_59H VH and VL. In some embodiments of the isolated monoclonal antibody or antigen-binding fragment thereof described herein, the VH comprises an amino acid sequence that is at least about 80%, about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54Q VH. In some embodiments, the VH comprises an amino acid sequence that is at least about 80% identical to the PC68-L31_54Q VH. In some embodiments, the VH comprises an amino acid sequence that is at least about 90% identical to the PC68-L31_54Q VH. In some embodiments, the VH comprises an amino acid sequence that is at least about 95% identical to the PC68-L31_54Q VH. In some embodiments, the VH comprises an amino acid sequence that is at least about 97% identical to the PC68-L31_54Q VH. In some embodiments, the VH comprises an amino acid sequence that is identical to the PC68-L31_54Q VH. In some embodiments, the VL comprises an amino acid sequence that is at least about 80%, about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54Q VL. In some embodiments, the VL comprises an amino acid sequence that is at least about 80% identical to the PC68-L31_54Q VL. In some embodiments, the VL comprises an amino acid sequence that is at least about 90% identical to the PC68-L31_54Q VL. In some embodiments, the VL comprises an amino acid sequence that is at least about 95% identical to the PC68-L31_54Q VL. In some embodiments, the VL comprises an amino acid sequence that is at least about 97% identical to the PC68-L31_54Q VL. In some embodiments, the VL comprises an amino acid sequence that is identical to the PC68-L31_54Q VL. In some embodiments, the VH and VL comprise an amino acid sequence that is at least about 80%, about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54Q VH and VL. In some embodiments, the VH and VL comprise an amino acid sequence that is at least about 80% identical to the PC68-L31_54Q VH and VL. In some embodiments, the VH and VL comprise an amino acid sequence that is at least about 90% identical to the PC68-L31_54Q VH and VL. In some embodiments, the VH and VL comprise an amino acid sequence that is at least about 95% identical to the PC68-L31_54Q VH and VL. In some embodiments, the VH and VL comprise an amino acid sequence that is at least about 97% identical to the PC68-L31_54Q VH and VL. In some embodiments, the VH and VL comprise the PC68-L31_54Q VH and VL.In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding a HIV Env trimer and comprises a heavy chain variable region (VH), wherein the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68- L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68- L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68- L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68- L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH. In some embodiments, the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54Q VH. In some embodiments, the VH comprises a VH CDR1, VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68- L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68- L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68- L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68- L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR1, VH CDR2, and VH CDR3, respectively. In some embodiments, VH comprises the PC68-L31_54Q VH CDR1, VH CDR2, and VH CDR3. In some embodiments, theVH CDR1, VH CDR2, and / or VH CDR3 is according to Kabat. In some embodiments, the VH CDR1, VH CDR2, and / or VH CDR3 is according to Table 1. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 is according to Kabat. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 is according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In some embodiments, the isolated monoclonal antibody or antigen-binding fragment described herein further comprises a light chain variable region (VL), wherein the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL. In some embodiments, the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54Q VL. In some embodiments, the VL comprises a VL CDR1, VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P,PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR1, VL CDR2, and VL CDR3, respectively. In some embodiments, the VL comprises the PC68-L31_54Q VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL CDR1, VL CDR2, and / or VL CDR3 is according to Kabat. In some embodiments, the VL CDR1, VL CDR2, and / or VL CDR3 is according to Table 1. In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 is according to Kabat. In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 is according to Table 1. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding a HIV Env trimer and comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68- L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, or PC68-L31_59H VH and VL. In some embodiments, the VH comprises a VH CDR1, VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR1, VH CDR2, and VH CDR3, respectively. In some embodiments, the VH comprises a VH CDR1, VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, and VH CDR3, respectively. In some embodiments, the VL comprises a VL CDR1, VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68- L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68- L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68- L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68- L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR1, VL CDR2, and VL CDR3, respectively. In some embodiments, the VL comprises a VL CDR1, VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_54Q VL CDR1, VL CDR2, and VL CDR3, respectively. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 is according to Kabat. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 is according to Table 1. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 is according to Kabat. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 is according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding a HIV Env trimer and comprises a heavy chain variableregion (VH) and a light chain variable region (VL), wherein the VH and VL comprises the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68- L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, or PC68-L31_59H VH and VL. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_32A. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32A VH. In some embodiments, the VH comprises the PC68-L31_32A VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_32A VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32A VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32A VL. In some embodiments, the VL comprises the PC68- L31_32A VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_32A VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32A VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_32A VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_32A VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env.In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_32B. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32B VH. In some embodiments, the VH comprises the PC68-L31_32B VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_32B VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32B VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32B VL. In some embodiments, the VL comprises the PC68- L31_32B VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_32B VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32B VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_32B VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_32B VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_32C. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32C VH. In some embodiments, the VH comprises the PC68-L31_32C VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_32C VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32C VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32C VL. In some embodiments, the VL comprises the PC68- L31_32C VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_32C VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32C VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_32C VH CDR1, VH CDR2, VH CDR3, VL CDR1, VLCDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_32C VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_32D. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32D VH. In some embodiments, the VH comprises the PC68-L31_32D VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_32D VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32D VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32D VL. In some embodiments, the VL comprises the PC68- L31_32D VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_32D VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32D VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_32D VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_32D VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_32E. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32E VH. In some embodiments, the VH comprises the PC68-L31_32E VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_32E VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32E VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32E VL. In some embodiments, the VL comprises the PC68-L31_32E VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_32E VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32E VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_32E VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_32E VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_32F. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32F VH. In some embodiments, the VH comprises the PC68-L31_32F VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_32F VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32F VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32F VL. In some embodiments, the VL comprises the PC68- L31_32F VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_32F VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32F VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_32F VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_32F VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_32G. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32G VH. In some embodiments, the VH comprises the PC68-L31_32G VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_32G VH CDR1,VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32G VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32G VL. In some embodiments, the VL comprises the PC68- L31_32G VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_32G VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32G VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_32G VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_32G VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_32H. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32H VH. In some embodiments, the VH comprises the PC68-L31_32H VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_32H VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32H VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32H VL. In some embodiments, the VL comprises the PC68- L31_32H VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_32H VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32H VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_32H VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_32H VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68-L31_32I. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32I VH. In some embodiments, the VH comprises the PC68-L31_32I VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_32I VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32I VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32I VL. In some embodiments, the VL comprises the PC68- L31_32I VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68- L31_32I VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32I VL. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_32I VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_32I VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_32J. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32J VH. In some embodiments, the VH comprises the PC68-L31_32J VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_32J VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32J VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32J VL. In some embodiments, the VL comprises the PC68- L31_32J VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68- L31_32J VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32J VL. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_32J VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_32J VH and VL. In some embodiments, the CDRs are according to Kabat. In someembodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_32K. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32K VH. In some embodiments, the VH comprises the PC68-L31_32K VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_32K VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32K VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32K VL. In some embodiments, the VL comprises the PC68- L31_32K VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_32K VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_32K VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_32K VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_32K VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_38A. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_38A VH. In some embodiments, the VH comprises the PC68-L31_38A VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_38A VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_38A VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_38A VL. In some embodiments, the VL comprises the PC68- L31_38A VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_38A VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at leastabout 90% identical to the PC68-L31_38A VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_38A VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_38A VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_38B. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_38B VH. In some embodiments, the VH comprises the PC68-L31_38B VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_38B VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_38B VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_38B VL. In some embodiments, the VL comprises the PC68- L31_38B VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_38B VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_38B VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_38B VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_38B VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_38C. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_38C VH. In some embodiments, the VH comprises the PC68-L31_38C VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_38C VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_38C VH. In some embodiments, the antibody or antigen-binding fragment furthercomprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_38C VL. In some embodiments, the VL comprises the PC68- L31_38C VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_38C VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_38C VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_38C VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_38C VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_38D. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_38D VH. In some embodiments, the VH comprises the PC68-L31_38D VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_38D VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_38D VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_38D VL. In some embodiments, the VL comprises the PC68- L31_38D VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_38D VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_38D VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_38D VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_38D VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_38E. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to thePC68-L31_38E VH. In some embodiments, the VH comprises the PC68-L31_38E VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_38E VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_38E VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_38E VL. In some embodiments, the VL comprises the PC68- L31_38E VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_38E VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_38E VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_38E VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_38E VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43A. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43A VH. In some embodiments, the VH comprises the PC68-L31_43A VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43A VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43A VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43A VL. In some embodiments, the VL comprises the PC68- L31_43A VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43A VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43A VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43A VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43A VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env.In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43B. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43B VH. In some embodiments, the VH comprises the PC68-L31_43B VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43B VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43B VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43B VL. In some embodiments, the VL comprises the PC68- L31_43B VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43B VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43B VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43B VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43B VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43C. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43C VH. In some embodiments, the VH comprises the PC68-L31_43C VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43C VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43C VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43C VL. In some embodiments, the VL comprises the PC68- L31_43C VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43C VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43C VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43C VH CDR1, VH CDR2, VH CDR3, VL CDR1, VLCDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43C VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43D. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43D VH. In some embodiments, the VH comprises the PC68-L31_43D VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43D VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43D VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43D VL. In some embodiments, the VL comprises the PC68- L31_43D VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43D VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43D VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43D VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43D VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43E. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43E VH. In some embodiments, the VH comprises the PC68-L31_43E VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43E VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43E VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43E VL. In some embodiments, the VL comprises the PC68-L31_43E VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43E VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43E VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43E VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43E VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43F. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43F VH. In some embodiments, the VH comprises the PC68-L31_43F VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43F VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43F VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43F VL. In some embodiments, the VL comprises the PC68- L31_43F VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43F VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43F VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43F VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43F VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43G. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43G VH. In some embodiments, the VH comprises the PC68-L31_43G VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43G VH CDR1,VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43G VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43G VL. In some embodiments, the VL comprises the PC68- L31_43G VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43G VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43G VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43G VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43G VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43H. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43H VH. In some embodiments, the VH comprises the PC68-L31_43H VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43H VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43H VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43H VL. In some embodiments, the VL comprises the PC68- L31_43H VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43H VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43H VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43H VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43H VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68-L31_43I. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43I VH. In some embodiments, the VH comprises the PC68-L31_43I VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43I VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43I VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43I VL. In some embodiments, the VL comprises the PC68- L31_43I VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68- L31_43I VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43I VL. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43I VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43I VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43J. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43J VH. In some embodiments, the VH comprises the PC68-L31_43J VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43J VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43J VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43J VL. In some embodiments, the VL comprises the PC68- L31_43J VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68- L31_43J VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43J VL. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43J VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43J VH and VL. In some embodiments, the CDRs are according to Kabat. In someembodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43K. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43K VH. In some embodiments, the VH comprises the PC68-L31_43K VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43K VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43K VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43K VL. In some embodiments, the VL comprises the PC68- L31_43K VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43K VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43K VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43K VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43K VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43L. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43L VH. In some embodiments, the VH comprises the PC68-L31_43L VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43L VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43L VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43L VL. In some embodiments, the VL comprises the PC68- L31_43L VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43L VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at leastabout 90% identical to the PC68-L31_43L VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43L VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43L VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43M. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43M VH. In some embodiments, the VH comprises the PC68-L31_43M VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43M VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43M VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43M VL. In some embodiments, the VL comprises the PC68-L31_43M VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43M VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43M VL. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43M VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43M VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43N. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43N VH. In some embodiments, the VH comprises the PC68-L31_43N VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43N VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43N VH. In some embodiments, the antibody or antigen-binding fragment furthercomprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43N VL. In some embodiments, the VL comprises the PC68- L31_43N VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43N VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43N VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43N VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43N VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43P. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43P VH. In some embodiments, the VH comprises the PC68-L31_43P VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43P VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43P VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43P VL. In some embodiments, the VL comprises the PC68- L31_43P VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43P VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43P VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43P VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43P VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43Q. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to thePC68-L31_43Q VH. In some embodiments, the VH comprises the PC68-L31_43Q VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43Q VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43Q VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43Q VL. In some embodiments, the VL comprises the PC68- L31_43Q VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43Q VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43Q VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43Q VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43Q VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43R. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43R VH. In some embodiments, the VH comprises the PC68-L31_43R VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43R VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43R VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43R VL. In some embodiments, the VL comprises the PC68- L31_43R VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43R VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43R VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43R VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43R VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env.In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_43S. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43S VH. In some embodiments, the VH comprises the PC68-L31_43S VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_43S VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43S VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_43S VL. In some embodiments, the VL comprises the PC68- L31_43S VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_43S VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_43S VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_43S VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_43S VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_49A. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_49A VH. In some embodiments, the VH comprises the PC68-L31_49A VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_49A VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_49A VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_49A VL. In some embodiments, the VL comprises the PC68- L31_49A VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_49A VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_49A VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_49A VH CDR1, VH CDR2, VH CDR3, VL CDR1, VLCDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_49A VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_49B. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_49B VH. In some embodiments, the VH comprises the PC68-L31_49B VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_49B VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_49B VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_49B VL. In some embodiments, the VL comprises the PC68- L31_49B VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_49B VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_49B VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_49B VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_49B VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_49C. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_49C VH. In some embodiments, the VH comprises the PC68-L31_49C VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_49C VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_49C VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_49C VL. In some embodiments, the VL comprises the PC68-L31_49C VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_49C VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_49C VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_49C VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_49C VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_49D. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_49D VH. In some embodiments, the VH comprises the PC68-L31_49D VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_49D VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_49D VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_49D VL. In some embodiments, the VL comprises the PC68- L31_49D VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_49D VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_49D VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_49D VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_49D VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_49E. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_49E VH. In some embodiments, the VH comprises the PC68-L31_49E VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_49E VH CDR1,VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_49E VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_49E VL. In some embodiments, the VL comprises the PC68- L31_49E VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_49E VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_49E VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_49E VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_49E VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54A. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54A VH. In some embodiments, the VH comprises the PC68-L31_54A VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54A VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54A VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54A VL. In some embodiments, the VL comprises the PC68- L31_54A VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54A VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54A VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54A VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54A VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68-L31_54B. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54B VH. In some embodiments, the VH comprises the PC68-L31_54B VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54B VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54B VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54B VL. In some embodiments, the VL comprises the PC68- L31_54B VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54B VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54B VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54B VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54B VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54C. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54C VH. In some embodiments, the VH comprises the PC68-L31_54C VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54C VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54C VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54C VL. In some embodiments, the VL comprises the PC68- L31_54C VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54C VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54C VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54C VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54C VH and VL. In some embodiments, the CDRs are according to Kabat. In someembodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54D. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54D VH. In some embodiments, the VH comprises the PC68-L31_54D VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54D VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54D VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54D VL. In some embodiments, the VL comprises the PC68- L31_54D VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54D VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54D VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54D VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54D VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54E. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54E VH. In some embodiments, the VH comprises the PC68-L31_54E VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54E VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54E VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54E VL. In some embodiments, the VL comprises the PC68- L31_54E VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54E VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at leastabout 90% identical to the PC68-L31_54E VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54E VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54E VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54F. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54F VH. In some embodiments, the VH comprises the PC68-L31_54F VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54F VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54F VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54F VL. In some embodiments, the VL comprises the PC68- L31_54F VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54F VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54F VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54F VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54F VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54G. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54G VH. In some embodiments, the VH comprises the PC68-L31_54G VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54G VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54G VH. In some embodiments, the antibody or antigen-binding fragment furthercomprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54G VL. In some embodiments, the VL comprises the PC68- L31_54G VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54G VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54G VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54G VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54G VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54H. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54H VH. In some embodiments, the VH comprises the PC68-L31_54H VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54H VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54H VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54H VL. In some embodiments, the VL comprises the PC68- L31_54H VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54H VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54H VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54H VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54H VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54I. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to thePC68-L31_54I VH. In some embodiments, the VH comprises the PC68-L31_54I VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54I VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54I VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54I VL. In some embodiments, the VL comprises the PC68- L31_54I VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68- L31_54I VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54I VL. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54I VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54I VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54J. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54J VH. In some embodiments, the VH comprises the PC68-L31_54J VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54J VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54J VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54J VL. In some embodiments, the VL comprises the PC68- L31_54J VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68- L31_54J VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54J VL. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54J VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54J VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env.In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54K. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54K VH. In some embodiments, the VH comprises the PC68-L31_54K VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54K VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54K VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54K VL. In some embodiments, the VL comprises the PC68- L31_54K VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54K VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54K VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54K VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54K VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54L. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54L VH. In some embodiments, the VH comprises the PC68-L31_54L VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54L VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54L VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54L VL. In some embodiments, the VL comprises the PC68- L31_54L VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54L VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54L VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54L VH CDR1, VH CDR2, VH CDR3, VL CDR1, VLCDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54L VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54M. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54M VH. In some embodiments, the VH comprises the PC68-L31_54M VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54M VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54M VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54M VL. In some embodiments, the VL comprises the PC68-L31_54M VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54M VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54M VL. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54M VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54M VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54N. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54N VH. In some embodiments, the VH comprises the PC68-L31_54N VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54N VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54N VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54N VL. In some embodiments, the VL comprises the PC68-L31_54N VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54N VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54N VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54N VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54N VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54P. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54P VH. In some embodiments, the VH comprises the PC68-L31_54P VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54P VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54P VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54P VL. In some embodiments, the VL comprises the PC68- L31_54P VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54P VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54P VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54P VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54P VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54Q. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54Q VH. In some embodiments, the VH comprises the PC68-L31_54Q VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54Q VH CDR1,VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54Q VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54Q VL. In some embodiments, the VL comprises the PC68- L31_54Q VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54Q VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54Q VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54Q VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54Q VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_54R. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54R VH. In some embodiments, the VH comprises the PC68-L31_54R VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54R VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54R VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54R VL. In some embodiments, the VL comprises the PC68- L31_54R VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54R VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54R VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54R VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54R VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68-L31_54S. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54S VH. In some embodiments, the VH comprises the PC68-L31_54S VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_54S VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54S VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_54S VL. In some embodiments, the VL comprises the PC68- L31_54S VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_54S VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_54S VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_54S VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_54S VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_59A. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59A VH. In some embodiments, the VH comprises the PC68-L31_59A VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_59A VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59A VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59A VL. In some embodiments, the VL comprises the PC68- L31_59A VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_59A VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59A VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_59A VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_59A VH and VL. In some embodiments, the CDRs are according to Kabat. In someembodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_59B. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59B VH. In some embodiments, the VH comprises the PC68-L31_59B VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_59B VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59B VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59B VL. In some embodiments, the VL comprises the PC68- L31_59B VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_59B VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59B VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_59B VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_59B VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_59C. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59C VH. In some embodiments, the VH comprises the PC68-L31_59C VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_59C VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59C VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59C VL. In some embodiments, the VL comprises the PC68- L31_59C VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_59C VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at leastabout 90% identical to the PC68-L31_59C VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_59C VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_59C VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_59D. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59D VH. In some embodiments, the VH comprises the PC68-L31_59D VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_59D VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59D VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59D VL. In some embodiments, the VL comprises the PC68- L31_59D VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_59D VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59D VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_59D VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_59D VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_59E. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59E VH. In some embodiments, the VH comprises the PC68-L31_59E VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_59E VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59E VH. In some embodiments, the antibody or antigen-binding fragment furthercomprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59E VL. In some embodiments, the VL comprises the PC68- L31_59E VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_59E VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59E VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_59E VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_59E VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_59F. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59F VH. In some embodiments, the VH comprises the PC68-L31_59F VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_59F VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59F VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59F VL. In some embodiments, the VL comprises the PC68- L31_59F VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_59F VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59F VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_59F VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_59F VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_59G. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to thePC68-L31_59G VH. In some embodiments, the VH comprises the PC68-L31_59G VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_59G VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59G VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59G VL. In some embodiments, the VL comprises the PC68- L31_59G VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_59G VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59G VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_59G VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_59G VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_59H. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59H VH. In some embodiments, the VH comprises the PC68-L31_59H VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_59H VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59H VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59H VL. In some embodiments, the VL comprises the PC68- L31_59H VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68-L31_59H VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59H VL. In some embodiments, the antibody or antigen- binding fragment comprises the PC68-L31_59H VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_59H VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env.In one aspect, provided herein is an isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds an HIV Env trimer and comprises the VH CDR3 of PC68- L31_59I. In some embodiments, the antibody or antigen-binding fragment comprises a VH having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59I VH. In some embodiments, the VH comprises the PC68-L31_59I VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the VH comprises the PC68-L31_59I VH CDR1, VH CDR2, and VH CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59I VH. In some embodiments, the antibody or antigen-binding fragment further comprises a VL having an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_59I VL. In some embodiments, the VL comprises the PC68- L31_59I VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the VL comprises the PC68- L31_59I VL CDR1, VL CDR2, and VL CDR3 and an amino acid sequence that is at least about 90% identical to the PC68-L31_59I VL. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_59I VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the antibody or antigen-binding fragment comprises the PC68-L31_59I VH and VL. In some embodiments, the CDRs are according to Kabat. In some embodiments, the CDRs are according to Table 1. In some embodiments, the HIV Env is BG505 HIV Env. In some embodiments of the isolated monoclonal antibody described herein, the antibody is not the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68- L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68- L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68- L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68- L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, or PC68-L31_59H antibody. In some embodiments, the antibody is not PC68-L31_54Q.In some embodiments, an antibody described herein comprises a VH CDR3 comprising a sequence that is not identical to the VHCDR3 of any of the VH regions shown in Table 2. In some embodiments, an antibody described herein comprises a VH CDR1, VH CDR2, or VH CDR3 comprising an amino acid sequence that is not identical to the amino acid sequence of VH CDR1, VH CDR2, or VH CDR3 of any of the VH regions shown in Table 2. In some embodiments, an antibody described herein comprises a VL CDR1, VL CDR2, or VL CDR3 comprising an amino acid sequence that is not identical to the amino acid sequence of VL CDR1, VL CDR2, or VL CDR3 of any of the VL regions shown in Table 2. In some embodiments, an antibody described herein comprises a VH comprising an amino acid sequence that is not identical to the amino acid sequence of any VH region shown in Table 2. In some embodiments, an antibody described herein comprises a VL comprising an amino acid sequence that is not identical to the amino acid sequence of any VL region shown in Table 2. In some embodiments, an antibody described herein comprises a VH that is markedly different from the VH regions shown in Table 2. In some embodiments, an antibody described herein comprises a VL that is markedly different from the VL regions shown in Table 2. In some embodiments, an antibody described herein comprises at least one substitution, insertion, or deletion compared to the corresponding amino acid sequence of any of the VH and VL regions shown in Table 2. In some embodiments, the monoclonal antibody or antigen-binding fragment described herein further comprises a heavy and / or light chain constant region. In some embodiments, the monoclonal antibody or antigen-binding fragment comprises a heavy chain constant region. In some embodiments, the monoclonal antibody or antigen-binding fragment comprises a light chain constant region. In some embodiments, the monoclonal antibody or antigen-binding fragment comprises a heavy and light chain constant region. In some embodiments, the heavy and / or light chain constant region is a human heavy and / or light chain constant region. In some embodiments, the heavy and light chain constant region are a human heavy and light chain constant region. In some embodiments, the heavy chain constant region is selected from the group consisting of a human immunoglobulin IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2 constant region. In some embodiments, the heavy chain constant region comprises a native amino acid sequence. In some embodiments, the heavy chain constant region comprises a non-native variant amino acid sequence. In some embodiments, the isolated monoclonal antibody or antigen-binding fragment described herein is a recombinant antibody, a chimeric antibody, a human antibody, an antibody fragment, a bispecific antibody, or a trispecific antibody. In some embodiments, the antibodyfragment comprises a single-chain Fv (scFv), Fab fragment, F(ab’)2 fragment, or an isolated VH domain. In some embodiments, the antibody is a bispecific antibody. In some embodiments, the antibody is a trispecific antibody. In some embodiments, the antibody or antigen-binding fragment thereof described herein competes with a reference antibody for binding to the HIV Env trimer, wherein the reference antibody is selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68- L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68- L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68- L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68- L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68- L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H antibody. In some embodiments, the trimer is an SOSIP trimer. In some embodiments, the HIV Env is BG505 HIV Env. In some embodiments, the reference antibody is the PC68-L31_54Q antibody. In some embodiments, the antibody or antigen-binding fragment thereof described herein binds to the same epitope of the HIV Env trimer as a reference antibody selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P,PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H antibody. In some embodiments, the trimer is an SOSIP trimer. In some embodiments, the HIV Env is BG505 HIV Env. In some embodiments, the reference antibody is the PC68-L31_54Q antibody. In some embodiments of the antibody or antigen-binding fragment thereof described herein the HIV Env is BG505 HIV Env. In some embodiments of the antibody or antigen-binding fragment thereof described herein the antibody or antigen-binding fragment is capable of neutralizing at least 6 HIV isolates in the 13-member indicator virus panel. In some embodiments of the antibody or antigen-binding fragment thereof described herein the antibody or antigen-binding fragment is capable of neutralizing at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95% or 100% of the HIV isolates in the 119-member indicator virus panel. In some embodiments of the antibody or antigen-binding fragment thereof described herein the antibody or antigen-binding fragment is capable of neutralizing the HIV isolates with a median IC50 equal to or less than about 1 µg / ml, about 0.8 µg / ml, 0.5 µg / ml, or 0.3 µg / ml. In some embodiments, an antibody or antibody fragment described herein neutralizes a pseudovirus produced in the presence of kifunensine better than those with wildtype glycoforms. In some embodiments, the antibody has a lowed IC50 value against a pseudovirus produced in the presence of kifunensine than against the corresponding pseudovirus comprising wildtype glycoforms. In some embodiments, the antibody has a lowed IC80 value against a pseudovirus produced in the presence of kifunensine than against the corresponding pseudovirus comprising wildtype glycoforms. In some embodiments, an antibody or antibody fragment described herein can neutralize a pseudovirusvirus comprising a single substitution in the Env polypeptide selected from the group consisting of N197A, N234A, N262A, N276A, N301A, N363A, N386A and N462A with the same or lower IC50 than a corresponding pseudovirus that does not comprise the substitution. In some embodiments, an antibody or antibody fragment described herein can neutralize a pseudovirusvirus comprising the N197A Env substitution with the same or lower IC50 than a corresponding pseudovirus that does not comprise the substitution. In some embodiments, an antibody or antibody fragment described herein can neutralize a pseudovirusvirus comprising the N234A Env substitution with the same or lower IC50 than a corresponding pseudovirus that does not comprisethe substitution. In some embodiments, an antibody or antibody fragment described herein can neutralize a pseudovirusvirus comprising the N262A Env substitution with the same or lower IC50 than a corresponding pseudovirus that does not comprise the substitution. In some embodiments, an antibody or antibody fragment described herein can neutralize a pseudovirusvirus comprising the N276A Env substitution with the same or lower IC50 than a corresponding pseudovirus that does not comprise the substitution. In some embodiments, an antibody or antibody fragment described herein can neutralize a pseudovirusvirus comprising the N301A Env substitution with the same or lower IC50 than a corresponding pseudovirus that does not comprise the substitution. In some embodiments, an antibody or antibody fragment described herein can neutralize a pseudovirusvirus comprising the N363A Env substitution with the same or lower IC50 than a corresponding pseudovirus that does not comprise the substitution. In some embodiments, an antibody or antibody fragment described herein can neutralize a pseudovirusvirus comprising the N386A Env substitution with the same or lower IC50 than a corresponding pseudovirus that does not comprise the substitution. In some embodiments, an antibody or antibody fragment described herein can neutralize a pseudovirusvirus comprising the N462A Env substitution with the same or lower IC50 than a corresponding pseudovirus that does not comprise the substitution. In some embodiments, an antibody or antibody fragment described herein is capable of neutralizing at least two cross-clade isolates of HIV. In some embodiments, the antibody is capable of neutralizing at least one clade B isolate and at least one clade AG isolate. In some embodiments, the antibody is capable of neutralizing at least one clade B isolate and at least one clade AC isolate. In some embodiments, an antibody or antigen-binding fragment thereof described herein is a broadly neutralizing antibody. In some embodiments, an antibody or antigen-binding fragment thereof described herein neutralizes 2, 3, 4, 5, 6, 7, 8, 9, or more HIV strains or pseudoviruses that belong to the same or different clades. In some embodiments, an antibody described herein is capable of neutralizing HIV strains or pseudoviruses from at least two different clades. In some embodiments, an antibody described herein is capable of neutralizing at least one clade B strain or pseudovirus and one clade AG strain or pseudovirus. In some embodiments, an antibody described herein is capable of neutralizing at least one clade B strain or pseudovirus and one clade AC strain or pseudovirus. In some embodiments, an antibody described herein is capable of neutralizing more than one clade B strain or pseudovirus.In some embodiments, the antibody is a broadly neutralizing antibody. In some embodiments, the antibody specifically binds an Env trimer of at least one HIV isolate in the 13- member indicator virus panels of Figure 1. In some embodiments, the antibody specifically binds an Env trimer of at least two, at least three, at least four, or at least five HIV isolates in the 13- member indicator virus panel of Figure 1. In some embodiments, the antibody specifically binds an Env trimer of at least one HIV isolate in the 119-member indicator virus panels of Table 4. In some embodiments, the antibody specifically binds an Env trimer of at least 30%, at least 40% or at least 50% of the HIV isolates in the 119-member indicator virus panel of Table 4. In some embodiments, an antibody or antigen-binding fragment thereof described herein is a recombinant antibody, a chimeric antibody, an antibody fragment, a bispecific antibody, or a trispecific antibody. In some embodiments, an antibody or antigen-binding fragment thereof described herein is a bispecific antibody or a trispecific antibody. In some embodiments, the antibody or antigen-binding fragment thereof is a human antibody. In some embodiments, the antibody is a chimeric antibody. In some embodiments, an antibody or antigen-binding fragment thereof described herein is not polyreactive. In some embodiments, an isolated monoclonal antibody described herein further comprises heavy and / or light chain constant regions. In some embodiments, an isolated monoclonal antibody described herein further comprises human heavy and / or light chain constant regions. In some embodiments, the heavy chain constant region is selected from the group consisting of human immunoglobulins IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. In some embodiments, the heavy chain constant region comprises a native amino acid sequence. In some embodiments, the heavy chain constant region comprises a non-native variant amino acid sequence. In some embodiments, an antibody described herein is a recombinant antibody, a chimeric antibody, a bispecific antibody, a trispecific antibody, or a multispecific antibody. In some embodiments, the antibody fragment comprises a single-chain Fv (scFv), F(ab) fragment, F(ab’)2fragment, or an isolated VH domain. In some embodiments, an antibody described herein is a multispecific antibody, e.g. a bispecific antibody. Multispecific antibodies are monoclonal antibodies that have bindingspecificities for at least two different sites. In some embodiments, one of the binding specificities is for HIV Env and the other is for any other antigen. In some embodiments, bispecific antibodies bind to two different epitopes of HIV Env. Bispecific antibodies can be prepared as full length antibodies or antibody fragments. Techniques for making multispecific antibodies, e.g., bispecific antibodies include, but are not limited to, recombinant co-expression of two immunoglobulin heavy chain-light chain pairs having different specificities (see Milstein and Cuello, Nature 305: 537 (1983)), WO 93 / 08829, and Traunecker A., et al., EMBO J. 10: 3655 (1991)), and "knob-in-hole" engineering (see, e.g., U.S. Patent No. 5,731,168). Multi-specific antibodies may also be made by engineering electrostatic steering effects for making antibody Fc-heterodimeric molecules (WO 2009 / 089004A1); cross-linking two or more antibodies or fragments (see, e.g., US Patent No. 4,676,980, and Brennan et al., Science, 229: 81 (1985)); using leucine zippers to produce bi-specific antibodies (see, e.g., Kostelny et al., J. Immunol., 148(5):1547-1553 (1992)); using "diabody" technology for making bispecific antibody fragments (see, e.g., Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993)); and using single-chain Fv (scFv) dimers (see, e.g. Gruber et al., J. Immunol., 152:5368 (1994)); and preparing trispecific antibodies as described, e.g., in Tutt et al. J. Immunol. 147: 60 (1991). Engineered antibodies with three or more functional antigen-binding sites, including "Octopus antibodies" and dual variable domain (DVD) immunoglobulins are also included herein (see, e.g. US 2006 / 0025576A1 and US Patent 10,093,733). The antibody or fragment described herein also includes a "Dual Acting Fab" or "DAF" comprising an antigen- binding site that binds to different epitopes, e.g., two different HIV Env epitopes (see, US 2008 / 0069820, for example). In some embodiments, an antibody described herein is a multispecific antibody, e.g. a bispecific antibody comprising a first antigen-binding domain comprising a VH domain or VH and VL domains described herein, and a second antigen-binding region capable of binding an HIV Env epitope. In some embodiments, the second antigen-binding region binds to an HIV Env epitope region different from the HIV Env epitope region bound by an antibody described herein. In some embodiments, the second agent is one or more anti-HIV Env antibody that binds to the CD4 binding site (CD4bs), V2 apex, N332 / V3 base supersite, fusion peptide (FP), silent face, gp120-gp41 interface or membrane-proximal external region (MPER). In some embodiments, the second agent is one or more anti-HIV Env antibody that binds to the CD4 binding site (CD4bs), V2 apex, silent face, fusion peptide (FP), gp120-gp41 interface or membrane-proximal external region (MPER).In some embodiments, the second antigen-binding region binds to the CD4 binding site (CD4bs) epitope region. In some embodiments, the second antigen-binding region binds to the V2 apex. In some embodiments, the second antigen-binding region binds to the N332 / V3 base supersite. In some embodiments, the second antigen-binding region binds to the gp120-gp41 interface epitope region. In some embodiments, the second antigen-binding region binds to the silent face. In some embodiments, the second antigen-binding region binds to fusion peptide (FP). In some embodiments, the second antigen-binding region binds to the membrane-proximal external region (MPER). In some embodiments, an antibody described herein comprises a heavy and / or light chain constant region. In some embodiments, an antibody described herein comprises a human heavy and / or light chain constant region. In some embodiments, the heavy chain constant...
Claims
CLAIMS What is claimed is:
1. An isolated monoclonal antibody or antigen-binding fragment thereof that binds to an HIV Env trimer, does not bind to the corresponding monomeric gp120 polypeptide of the HIV Env and competes with VRC01 for binding to the HIV Env trimer, optionally wherein the trimer is an SOSIP trimer, and optionally wherein the HIV Env is BG505 HIV Env.
2. An isolated monoclonal antibody or antigen-binding fragment thereof which binds to an HIV Env trimer, does not bind to the corresponding monomeric gp120 polypeptide of the HIV Env and competes with a reference antibody for binding to the HIV Env trimer, wherein the reference antibody is selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68- L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68- L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68- L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68- L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68- L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H antibody, optionally wherein the trimer is an SOSIP trimer, and optionally wherein the HIV Env is BG505 HIV Env.
3. The antibody or antigen-binding fragment of claim 2, wherein the reference antibody is the PC68- L31_54Q antibody.
4. An isolated monoclonal antibody or antigen-binding fragment thereof which binds to the same epitope of an HIV Env trimer as a reference antibody selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H antibody, optionally wherein the trimer is an SOSIP trimer, and optionally wherein the HIV Env is BG505 HIV Env.
5. The antibody or antigen-binding fragment of claim 4, wherein the reference antibody is the PC68- L31_54Q antibody.
6. The antibody or antigen-binding fragment of any one of claims 1 to 5, which neutralizes a pseudovirus produced in the presence of kifunensine better than those with wildtype glycoforms.
7. The antibody or antigen-binding fragment of any one of claims 1 to 6, which neutralizes a pseudovirusvirus comprising a single mutation in the Env polypeptide selected from the group consisting of N197A, N234A, N262A, N276A, N301A, N363A, N386A and N462A with the same or lower IC50 than a corresponding pseudovirus that does not comprise the mutation.
8. The antibody or antigen-binding fragment of any one of claims 1 to 7 which comprises (a) a VH and VL of the VH3-30 VL3-21 lineage, respectively; and (b) a VH CDR2 comprising a 5 amino acid insertion comprising the sequence of (V / I / L / P)(H / N / Q)(E / D)(Y / D / E)D (SEQ ID NO: 1261), wherein the insertion is between Kabat position 52 and 53.
9. The antibody or antigen-binding fragment of any one of claims 1 to 7 which comprises (a) a VH CDR2 comprising the amino acid sequence of (D / H)(A / G / V / M)G(V / I / L / P)(H / N / Q)(E / D)(Y / D / E / H)D(V / T / I / L / A)(K / I / E)(H / Y / G / Q) (SEQ ID NO: 1262); (b) a VH CDR3 comprising the amino acid sequence of (A / G)KD(S / F / Y / L / I / V / R)(F / V / I / R)(A / T / P / G)(Y / F / L)(Y / W / H / R)(G / S / D / A)(Y / T)(N / S / K / R / G / H)GP(H / Y / E / D / Q)(S / V / I / T) (SEQ ID NO: 1263); and (c) a VL CDR3 comprising the amino acid sequence of (Y / H / Q / F)(M / I / V)W(D / H)G(S / R)(G / I / L / R)(V / A / P / S / L)(R / H / G) (SEQ ID NO: 1264) 10. The antibody or antigen-binding fragment of any one of claims 1 to 9 comprising a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR3 comprising 0, 1, 2, 3, 4 or 5 substitutions.
11. The antibody or antigen-binding fragment of claim 10, wherein the VH CDR3 comprises the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68- L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR3.
12. The antibody or antigen-binding fragment of claim 10, wherein the VH CDR3 comprises the PC68- L31_54Q VH CDR3.
13. The antibody or antigen-binding fragment of any one of claims 1 to 12 comprising a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, wherein the VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR3 comprising 0, 1, 2, 3, 4 or 5 substitutions.
14. The antibody or antigen-binding fragment of claim 13, wherein the VL CDR3 comprises the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68- L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR3.
15. The antibody or antigen-binding fragment of claim 13, wherein the VL CDR3 comprises the PC68- L31_54Q VL CDR3.
16. The antibody or antigen-binding fragment of any one of claims 1 to 15 comprising a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 selected independently from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, PC68-L31_59H, and PC68-L31_59I VH CDR1s, VH CDR2s, VH CDR3s, VL CDR1s, VL CDR2s, and VL CDR3s.
17. The antibody or antigen-binding fragment of claim 16, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises (i) the VH CDR1, VH CDR2, and VH CDR3 of a VH selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68- L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68- L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68- L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68- L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68- L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, and PC68-L31_59H VHs and (ii) a VL CDR1, VL CDR2, and VL CDR3 of a VL selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68- L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68- L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68- L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68- L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, and PC68-L31_59I VLs.
18. The antibody or antigen-binding fragment of claim 17, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a VH / VL pair selected from the group consisting of the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68- L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H VH / VL pairs.
19. The antibody or antigen-binding fragment of claim 18, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3.
20. The antibody or antigen-binding fragment of claim 18, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_43J VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3.
21. The antibody or antigen-binding fragment of any one of claims 1 to 20, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 is according to Kabat.
22. The antibody or antigen-binding fragment of any one of claims 1 to 20, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 is according to Table 1.
23. The antibody or antigen-binding fragment of any one of claims 1 to 22 comprising a VH and a VL, wherein (a) the VH comprises an amino acid sequence having at least about 90%, 95%, 97%, 98%, 99% or 100% identity to a VH selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, and PC68-L31_59H VHs and (b) the VL comprises an amino acid sequence having at least about 90%, 95%, 97%, 98%, 99% or 100% identity to a VL selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, and PC68-L31_59I VLs.
24. The antibody or antigen-binding fragment of claim 23, wherein the VH and VL comprises a VH / VL pair selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68- L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68- L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68- L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68- L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A,PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68- L31_59H VH / VL pairs.
25. The antibody or antigen-binding fragment of any one of claims 1 to 22 comprising a VH and a VL, wherein (i) the VH comprises an amino acid sequence having at least about 90%, 95%, 97%, 98%, 99% or 100% identity to the PC68-L31_54Q VH, and (ii) the VL comprises an amino acid sequence having at least about 90%, 95%, 97%, 98%, 99% or 100% identity to the PC68-L31_54Q VL.
26. The antibody or antigen-binding fragment of any one of claims 1 to 22 comprising a VH and a VL, wherein the VH and VL comprises an amino acid sequence having at least about 90%, 95%, 97%, 98%, 99% or 100% identity to the PC68-L31_54Q VH and VL, respectively.
27. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding HIV Env and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68- L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68- L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68- L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68- L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions.
28. The isolated monoclonal antibody or antigen-binding fragment of claim 27, wherein the VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR3.
29. The isolated monoclonal antibody or antigen-binding fragment of claim 27 or claim 28, wherein the VH CDR3 is according to Kabat.
30. The isolated monoclonal antibody or antigen-binding fragment of claim 27 or claim 28, wherein the VH CDR3 is according to Table 1.
31. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein(a) the VH CDR1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH CDR1 comprising 0, 1, 2, 3, 4, or 5 substitutions; (b) the VH CDR2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH CDR2 comprising 0, 1, 2, 3, 4, or 5 substitutions; and (c) the VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions.
32. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein (a) the VH CDR1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH CDR1; (b) the VH CDR2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH CDR2; and (c) the VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH CDR3.
33. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein. (a) the VH CDR1 comprises the PC68-L31_54Q VH CDR1 comprising 0, 1, 2, 3, 4, or 5 substitutions; (b) the VH CDR2 comprises the PC68-L31_54Q VH CDR2 comprising 0, 1, 2, 3, 4, or 5 substitutions; and(c) the VH CDR3 comprises the PC68-L31_54Q VH CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions.
34. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein (a) the VH CDR1 comprises the PC68-L31_54Q VH CDR1; (b) the VH CDR2 comprises the PC68-L31_54Q VH CDR2; and (c) the VH CDR3 comprises the PC68-L31_54Q VH CDR3.
35. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68- L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68- L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68- L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68- L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68- L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR1, VH CDR2, and VH CDR3 independently comprising 0, 1, 2, 3, 4, or 5 substitutions.
36. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68- L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68- L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68- L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68- L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68- L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR1, VH CDR2, and VH CDR3.
37. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, and VH CDR3 independently comprising 0, 1, 2, 3, 4, or 5 substitutions.
38. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, and VH CDR3.
39. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 31 to 38, wherein the VH CDR1, VH CDR2, and VH CDR3 are according to Kabat.
40. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 31 to 38, wherein the VH CDR1, VH CDR2, and VH CDR3 are according to Table 1.
41. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 31 to 40, wherein (a) the VL CDR1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL CDR1 comprising 0, 1, 2, 3, 4 or 5 substitutions; (b) the VL CDR2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL CDR2 comprising 0, 1, 2, 3, 4 or 5 substitutions; and (c) the VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL CDR3 comprising 0, 1, 2, 3, 4 or 5 substitutions.
42. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 31 to 40, wherein (a) the VL CDR1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL CDR1; (b) the VL CDR2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL CDR2; and (c) the VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL CDR3.
43. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 31 to 40, wherein (a) the VL CDR1 comprises the PC68-L31_54Q VL CDR1 comprising 0, 1, 2, 3, 4, or 5 substitutions; (b) the VL CDR2 comprises the PC68-L31_54Q VL CDR2 comprising 0, 1, 2, 3, 4, or 5 substitutions; and (c) the VL CDR3 comprises the PC68-L31_54Q VL CDR3 comprising 0, 1, 2, 3, 4, or 5 substitutions.
44. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 31 to 40, wherein (a) the VL CDR1 comprises the PC68-L31_54Q VL CDR1; (b) the VL CDR2 comprises the PC68-L31_54Q VL CDR2; and (c) the VL CDR3 comprises the PC68-L31_54Q VL CDR3.
45. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 31 to 40, wherein the VL CDR1, VL CDR2 and VL CDR3 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR1, VL CDR2 and VL CDR3 independently comprising 0, 1, 2, 3, 4 or 5 substitutions.
46. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 31 to 40, wherein the VL CDR1, VL CDR2 and VL CDR3 comprises the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR1, VL CDR2 and VL CDR3.
47. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 31 to 40, wherein the VL CDR1, VL CDR2 and VL CDR3 comprises the PC68-L31_54Q VL CDR1, VL CDR2 and VL CDR3 independently comprising 0, 1, 2, 3, 4 or 5 substitutions.
48. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 31 to 40, wherein the VL CDR1, VL CDR2 and VL CDR3 comprises the PC68-L31_54Q VL CDR1, VL CDR2 and VL CDR3.
49. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 41 to 48, wherein the VL CDR1, VL CDR2, and VL CDR3 are according to Kabat.
50. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 41 to 48, wherein the VL CDR1, VL CDR2, and VL CDR3 are according to Table 1.
51. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, or PC68-L31_59H VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 independently comprising 0, 1, 2, 3, 4, or 5 substitutions.
52. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, or PC68-L31_59H VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3.
53. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 independently comprising 0, 1, 2, 3, 4, or 5 substitutions.
54. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region comprising a VH CDR1, VH CDR2, and VH CDR3 and a light chain variable region comprising a VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3.
55. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 51 to 54, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 are according to Kabat.
56. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 51 to 54, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 are according to Table 1.
57. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 27 to 56, wherein the VH comprises a VH FW1, VH FW2, VH FW3 and VH FW4 and the VL comprises a VL FW1, VL FW2, VL FW3 and VL FW4, and wherein (a) the VH FW1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH FW1 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions or deletions; (b) the VH FW2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH FW2 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions or deletions; (c) the VH FW3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH FW3 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions or deletions; and (d) the VH FW4 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH FW4 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions or deletions.
58. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 27 to 56, wherein the VH comprises a VH FW1, VH FW2, VH FW3 and VH FW4 and the VL comprises a VL FW1, VL FW2, VL FW3 and VL FW4, and wherein (a) the VH FW1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH FW1; (b) the VH FW2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH FW2; (c) the VH FW3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH FW3; and (d) the VH FW4 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59G, or PC68-L31_59H VH FW4.
59. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 27 to 56, wherein the VH comprises a VH FW1, VH FW2, VH FW3 and VH FW4 and the VL comprises a VL FW1, VL FW2, VL FW3 and VL FW4, and wherein the VH FW1, VH FW2, VH FW3 and VH FW4 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P,PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH FW1, VH FW2, VH FW3 and VH FW4.
60. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 27 to 56, wherein the VH comprises a VH FW1, VH FW2, VH FW3 and VH FW4 and the VL comprises a VL FW1, VL FW2, VL FW3 and VL FW4, and wherein the VH FW1, VH FW2, VH FW3 and VH FW4 comprises the PC68-L31_54Q VH FW1, VH FW2, VH FW3 and VH FW4.
61. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 57 to 60, wherein the VH FW1, VH FW2, VH FW3 and VH FW4 are according to Table 2.
62. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 27 to 61, wherein the VH comprises a VH FW1, VH FW2, VH FW3 and VH FW4 and the VL comprises a VL FW1, VL FW2, VL FW3 and VL FW4, and wherein (a) the VL FW1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL FW1 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions or deletions; (b) the VL FW2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL FW2 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions or deletions; (c) the VL FW3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL FW3 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions or deletions; and (d) the VL FW4 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL FW4 comprising 0, 1, 2, 3, 4, or 5 substitutions, insertions or deletions.
63. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 27 to 61, wherein the VH comprises a VH FW1, VH FW2, VH FW3 and VH FW4 and the VL comprises a VL FW1, VL FW2, VL FW3 and VL FW4, and wherein (a) the VL FW1 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I; (b) the VL FW2 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL FW2; (c) the VL FW3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL FW3; and (d) the VL FW4 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68- L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68- L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68- L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68- L31_59H, or PC68-L31_59I VL FW4.
64. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 27 to 61, wherein the VH comprises a VH FW1, VH FW2, VH FW3 and VH FW4 and the VL comprises a VL FW1, VL FW2, VL FW3 and VL FW4, and wherein the VL FW1, VL FW2, VL FW3 and VL FW4 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL FW1, VL FW2, VL FW3 and VL FW4.
65. The isolated monoclonal antibody or antigen-binding fragment thereof of any one of claims 27 to 61, wherein the VH comprises a VH FW1, VH FW2, VH FW3 and VH FW4 and the VL comprises a VL FW1, VL FW2, VL FW3 and VL FW4, and wherein the VL FW1, VL FW2, VL FW3 and VL FW4 comprises the PC68-L31_54Q VL FW1, VL FW2, VL FW3 and VL FW4.
66. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 57 to 65, wherein the VL FW1, VL FW2, VL FW3 and VL FW4 are according to Table 2.
67. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 27 to 66, wherein the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68- L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68- L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68- L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68- L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68- L31_59H VH.
68. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 27 to 67, wherein the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68- L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68- L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68- L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68- L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68- L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68- L31_59I VL.
69. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 27 to 66, wherein the VH and VL comprise the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68- L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68- L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68- L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, or PC68-L31_59H VH and VL.
70. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 27 to 69, wherein the VH and VL comprise the PC68-L31_54Q VH and VL.
71. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region (VH), wherein the VH comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH.
72. The isolated monoclonal antibody or antigen-binding fragment of claim 71, wherein the VH comprises a VH CDR1, VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR1, VH CDR2, and VH CDR3.
73. The isolated monoclonal antibody or antigen-binding fragment of claim 71, wherein the VH comprises a VH CDR1, VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, and VH CDR3.
74. The isolated monoclonal antibody or antigen-binding fragment of claim 72 or claim 73, wherein the VH CDR1, VH CDR2, and VH CDR3 are according to Kabat.
75. The isolated monoclonal antibody or antigen-binding fragment of claim 72 or claim 73, wherein the VH CDR1, VH CDR2, and VH CDR3 are according to Table 1.
76. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 71 to 75 further comprising a light chain variable region (VL), wherein the VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32A, PC68- L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G,PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68- L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68- L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68- L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68- L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68- L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL.
77. The isolated monoclonal antibody or antigen-binding fragment of claim 76, wherein the VL comprises a VL CDR1, VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR1, VL CDR2, and VL CDR3.
78. The isolated monoclonal antibody or antigen-binding fragment of claim 76, wherein the VL comprises a VL CDR1, VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_54Q VL CDR1, VL CDR2, and VL CDR3.
79. The isolated monoclonal antibody or antigen-binding fragment of claim 77 or claim 78, wherein the VH CDR1, VH CDR2, and VH CDR3 are according to Kabat.
80. The isolated monoclonal antibody or antigen-binding fragment of claim 77 or claim 78, wherein the VH CDR1, VH CDR2, and VH CDR3 are according to Table 1.
81. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL comprises an amino acid sequence that is at least about 90%, 95%, 97%, 98%, 99% or 100% identical to the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68- L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68- L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68- L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68- L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, or PC68-L31_59H VH and VL.
82. The isolated monoclonal antibody or antigen-binding fragment of claim 81, wherein the VH comprises a VH CDR1, VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68- L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68- L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68- L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68- L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68- L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68- L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59G, or PC68-L31_59H VH CDR1, VH CDR2, and VH CDR3.
83. The isolated monoclonal antibody or antigen-binding fragment of claim 81, wherein the VH comprises a VH CDR1, VH CDR2, and VH CDR3, wherein the VH CDR1, VH CDR2, and VH CDR3 comprises the PC68-L31_54Q VH CDR1, VH CDR2, and VH CDR3.
84. The isolated monoclonal antibody or antigen-binding fragment of claim 82 or claim 83, wherein the VH CDR1, VH CDR2, and VH CDR3 are according to Kabat.
85. The isolated monoclonal antibody or antigen-binding fragment of claim 82 or claim 83, wherein the VH CDR1, VH CDR2, and VH CDR3 are according to Table 1.
86. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 81 to 85, wherein the VL comprises a VL CDR1, VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68- L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68- L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68- L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68- L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, PC68-L31_59H, or PC68-L31_59I VL CDR1, VL CDR2, and VL CDR3.
87. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 81 to 85, wherein the VL comprises a VL CDR1, VL CDR2, and VL CDR3, wherein the VL CDR1, VL CDR2, and VL CDR3 comprises the PC68-L31_54Q VL CDR1, VL CDR2, and VL CDR3.
88. The isolated monoclonal antibody or antigen-binding fragment of claim 86 or claim 87, wherein the VL CDR1, VL CDR2, and VL CDR3 are according to Kabat.
89. The isolated monoclonal antibody or antigen-binding fragment of claim 86 or claim 87, wherein the VL CDR1, VL CDR2, and VL CDR3 are according to Table 1.
90. An isolated monoclonal antibody or antigen-binding fragment thereof that is capable of binding an HIV Env trimer and comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL comprises the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68- L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68- L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68- L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68- L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68- L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, or PC68- L31_59H VH and VL.
91. The isolated antibody of any one of claims 1 to 90, wherein the antibody is not the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68- L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68- L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68- L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68- L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68- L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68- L31_59E, PC68-L31_59F, or PC68-L31_59H antibody.
92. The monoclonal antibody or antigen-binding fragment of any one of claims 1 to 91, further comprising a heavy and / or light chain constant region.
93. The monoclonal antibody or antigen-binding fragment of any one of claims 1 to 91, further comprising a human heavy and / or light chain constant region.
94. The monoclonal antibody or antigen-binding fragment of claim 93, wherein the heavy chain constant region is selected from the group consisting of a human immunoglobulin IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2constant region.
95. The monoclonal antibody or antigen-binding fragment of any one of claims 92 to 94, wherein the heavy chain constant region comprises a native amino acid sequence.
96. The monoclonal antibody or antigen-binding fragment of any one of claims 92 to 94, wherein the heavy chain constant region comprises a non-native variant amino acid sequence.
97. The isolated monoclonal antibody or antigen-binding fragment of any one of claims 1 to 96, wherein the antibody is a recombinant antibody, a chimeric antibody, a human antibody, an antibody fragment, a bispecific antibody, or a trispecific antibody.
98. The isolated monoclonal antibody or antigen-binding fragment of claim 97, wherein the antibody fragment comprises a single-chain Fv (scFv), Fab fragment, F(ab’)2fragment, or an isolated VH domain.
99. The antibody or antigen-binding fragment of any one of claims 1 to 98, wherein the antibody is a bispecific antibody.
100. The antibody or antigen-binding fragment of any one of claims 1 to 98, wherein the antibody is a trispecific antibody.
101. The antibody or antigen-binding fragment thereof of any one of claims 27 to 100, which competes with a reference antibody for binding to the HIV Env trimer, wherein the reference antibody is selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68- L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68- L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68- L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68- L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68- L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68- L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H antibody, optionally wherein the trimer is an SOSIP trimer, and optionally wherein the HIV Env is BG505 HIV Env.
102. The antibody or antigen-binding fragment of claim 101, wherein the reference antibody is the PC68-L31_54Q antibody.
103. The antibody or antigen-binding fragment thereof of any one of claims 27 to 100, which binds to the same epitope of the HIV Env trimer as a reference antibody selected from the group consisting of the PC68-L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68- L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68-L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68- L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68-L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68- L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68-L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68- L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68-L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68- L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68-L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68- L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H antibody, optionally wherein the trimer is an SOSIP trimer, and optionally wherein the HIV Env is BG505 HIV Env.
104. The antibody or antigen-binding fragment of claim 103, wherein the reference antibody is the PC68-L31_54Q antibody.
105. The antibody or antigen-binding fragment thereof of any one of claims 1 to 104, wherein the HIV Env is BG505 HIV Env.
106. The antibody or antigen-binding fragment thereof of any one of claims 1 to 105, wherein the antibody is capable of neutralizing at least 6 HIV isolates in the 13-member indicator virus panel.
107. The antibody or antigen-binding fragment thereof of any one of claims 1 to 105, wherein the antibody is capable of neutralizing at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95% or 100% of the HIV isolates in the 119-member indicator virus panel.
108. The antibody or antigen-binding fragment thereof of claim 106 or 107, wherein the antibody is capable of neutralizing the HIV isolates with a median IC50equal to or less than about 1 µg / ml, about 0.8 µg / ml, 0.5 µg / ml, or 0.3 µg / ml.
109. A pharmaceutical composition comprising the antibody or antigen-binding fragment of any one of claims 1 to 108 and a pharmaceutically acceptable excipient.
110. An isolated polynucleotide encoding the antibody or antigen-binding fragment thereof of any one of claims 1 to 108.
111. The isolated polynucleotide of claim 110, which is a DNA.
112. The isolated polynucleotide of claim 110, which is an mRNA.
113. The isolated polynucleotide of claim 112, wherein the mRNA comprises a modified nucleotide.
114. A pharmaceutical composition comprising the isolated polynucleotide of any one of claims 110 to 113 and a pharmaceutically acceptable excipient.
115. An isolated vector comprising the polynucleotide of claim 110.
116. The isolated vector of claim 115, wherein the vector is a viral vector.
117. A recombinant virus comprising the polynucleotide of claim 110.
118. The recombinant virus of claim 117, which is a recombinant adeno-associated virus (AAV).
119. A pharmaceutical composition comprising the recombinant virus of claim 117 or claim 118 and a pharmaceutically acceptable excipient.
120. A host cell comprising the polynucleotide of claim 110 or the vector of claim 114.
121. The host cell of claim 118, which is E. coli, Pseudomonas, Bacillus, Streptomyces, yeast, CHO, YB / 20, NS0, PER-C6, HEK-293T, NIH-3T3, HeLa, BHK, Hep G2, SP2 / 0, R1.1, B-W, L-M, COS 1, COS 7, BSC1, BSC40, BMT10 cell, plant cell, insect cell, or human cell in tissue culture.
122. A method of producing the antibody or antigen-binding fragment of any one of claims 1 to 108 comprising culturing the host cell of claim 118 or claim 119 so that the antibody or antigen-binding fragment is expressed and the antibody or antigen-binding fragment is produced.
123. A method of neutralizing an HIV virus comprising contacting the virus with a sufficient amount of the antibody or antigen-binding fragment of any one of claims 1 to 108.
124. A method of reducing the likelihood of HIV infection in a subject exposed to HIV comprising administering to the subject a therapeutically sufficient amount of the antibody or antigen-binding fragment of any one of claims 1 to 108.
125. A method of reducing the likelihood of HIV infection in a subject exposed to HIV comprising administering to the subject a therapeutically sufficient amount of the pharmaceutical composition of claim 114 or claim 119.
126. A method of treating HIV / AIDS comprising administering to a subject in need thereof a therapeutically sufficient amount of the antibody or antigen-binding fragment thereof of any one of claims 1 to 108.
127. A method of treating HIV / AIDS comprising administering to a subject in need thereof a therapeutically sufficient amount of the pharmaceutical composition of claim 114 or claim 119.
128. A method of reducing viral load comprising administering to a subject in need thereof a therapeutically sufficient amount of the antibody or antigen-binding fragment thereof of any one of claims 1 to 108.
129. A method of reducing viral load comprising administering to a subject in need thereof a therapeutically sufficient amount of the pharmaceutical composition of claim 114 or claim 119.
130. The method of claims 124 to 129, wherein the administering to the subject is by at least one mode selected from oral, parenteral, subcutaneous, intramuscular, intravenous, vaginal, rectal, buccal, sublingual, and transdermal.
131. The method of any one of claims 124 to 129, further comprising administering at least one additional therapeutic agent.
132. The method of claim 131, wherein the additional therapeutic agent is an antiretroviral agent, a reservoir activator, or a second antibody.
133. The method of claim 131, wherein the additional therapeutic agent comprises a broadly neutralizing antibody.
134. The method of claim 131, wherein the additional therapeutic agent comprises two broadly neutralizing antibodies.
135. The method of claim 131, wherein the additional therapeutic agent comprises three broadly neutralizing antibodies.
136. A method for detecting HIV in a sample comprising contacting the sample with the antibody of any one of claims 1 to 108.
137. A method of purifying HIV from a sample comprising contacting the sample with the antibody of any one of claims 1 to 108.
138. A kit comprising the antibody of any one of claims 1 to 108, or the pharmaceutical composition of claim 114 and a) a detection reagent, b) an HIV antigen, c) a notice that reflects approval for use or sale for human administration, or d) any combination thereof.
139. A kit comprising the pharmaceutical composition of claim 114 or claim 119 and a) a detection reagent, b) an HIV antigen, c) a notice that reflects approval for use or sale for human administration, or d) any combination thereof.
140. A method of producing an engineered variant of an antibody of any one of claims 1 to 108 comprising (a) substituting one or more amino acid residues of the VH; and / or substituting one or more amino acid residues of the VL to create an engineered variant antibody, and (b) producing the engineered variant antibody.
141. The method of claim 140 wherein the antibody is selected from the group consisting of the PC68- L31_32A, PC68-L31_32B, PC68-L31_32C, PC68-L31_32D, PC68-L31_32E, PC68-L31_32F, PC68-L31_32G, PC68-L31_32H, PC68-L31_32I, PC68-L31_32J, PC68-L31_32K, PC68- L31_38A, PC68-L31_38B, PC68-L31_38C, PC68-L31_38D, PC68-L31_38E, PC68-L31_43A, PC68-L31_43B, PC68-L31_43C, PC68-L31_43D, PC68-L31_43E, PC68-L31_43F, PC68- L31_43G, PC68-L31_43H, PC68-L31_43I, PC68-L31_43J, PC68-L31_43K, PC68-L31_43L, PC68-L31_43M, PC68-L31_43N, PC68-L31_43P, PC68-L31_43Q, PC68-L31_43R, PC68- L31_43S, PC68-L31_49A, PC68-L31_49B, PC68-L31_49C, PC68-L31_49D, PC68-L31_49E, PC68-L31_54A, PC68-L31_54B, PC68-L31_54C, PC68-L31_54D, PC68-L31_54E, PC68- L31_54F, PC68-L31_54G, PC68-L31_54H, PC68-L31_54I, PC68-L31_54J, PC68-L31_54K, PC68-L31_54L, PC68-L31_54M, PC68-L31_54N, PC68-L31_54P, PC68-L31_54Q, PC68- L31_54R, PC68-L31_54S, PC68-L31_59A, PC68-L31_59B, PC68-L31_59C, PC68-L31_59D, PC68-L31_59E, PC68-L31_59F, and PC68-L31_59H antibody.
142. The method of claim 140 wherein the antibody is the PC68-L31_54Q antibody.