Single-domain antibodies and bispecific antibodies against HIV-1 and their use

Abstract

Bispecific antibodies that specifically bind to HIV-1 Env and neutralize HIV-1 are disclosed. Also provide are single-domain antibodies that specifically bind to HIV-1 Env and neutralize HIV-1. Nucleic acids encoding these bispecific and single-domain antibodies, vectors and host cells are also provided. In addition, the use of these bispecific and single-domain antibodies, nucleic acid molecules, and vectors to prevent and / or treat an HIV-1 infection is disclosed.

Description

[0001]4239-111089-02SINGLE-DOMAIN AND BISPECIFIC ANTIBODIES TO HIV-1 ENV AND THEIR USE CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No.63 / 558,539, filed February 27, 2024, which is incorporated by reference in its entirety. FIELD OF THE DISCLOSURE This relates to antibodies, including bispecific and single domain antibodies, that specifically bind to HIV-1 Env and their use, for example, in methods of treating a subject with HIV-1 infection. INCORPORATION OF ELECTRONIC SEQUENCE LISTING The electronic sequence listing is submitted as an XML file named “111089_Sequence_Listing.xml” (114,688 bytes), created on February 27, 2025, is herein incorporated by reference in its entirety. BACKGROUND Human Immunodeficiency Virus type 1 (HIV-1) infection, and the resulting Acquired Immunodeficiency Syndrome (AIDS), remain threats to global public health, despite extensive efforts to develop anti-HIV-1 therapeutic agents. An enveloped virus, HIV-1 hides from humoral recognition behind a wide array of protective mechanisms. The major HIV-1 envelope protein (HIV-1 Env) is a glycoprotein of approximately 160 kD (gp160). During infection, proteases of the host cell cleave gp160 into gp120 and gp41. Together gp120 and gp41 make up the HIV-1 envelope spike, which interacts with the host-cell receptor CD4 to facilitate virus infection, and is a target for neutralizing antibodies. Prior studies identified neutralizing monoclonal antibodies, including bispecific antibodies, that specifically bind HIV-1 Env. However, there is a need to develop additional neutralizing antibodies for HIV-1 with improved neutralization profiles for clinical treatment or prevention of HIV.4239-111089-02SUMMARY Disclosed herein are bispecific antibodies comprising a first binding domain that specifically binds to a V1-V2 region of HIV-1 Env and a second binding domain that specifically binds to a CD4 binding site on HIV-1 Env. The first binding domain comprises an antibody comprising a heavy chain variable region (VH) comprising a heavy chain complementarity determining region (HCDR)1, a HCDR2, and a HCDR3 of the VHsequence set forth as SEQ ID NO: 25 (CAP256V2LS), a light chain variable region (VL), and a constant domain. The second binding domain comprises a single-domain antibody or multimer thereof of wherein the single-domain antibody comprises the complementarity determining region 1 (CDR1), CDR2 and CDR3 of one of the single-domain antibody sequences set forth as (a) SEQ ID NO: 1 (G36), (b) SEQ ID NO: 5 (G36 K64E), (c) SEQ ID NO: 7 (R27), or (d) SEQ ID NO: 11 (R27 K64E). The C-terminus of the single domain antibody of the second binding domain is fused to the N terminus of the VL of the first binding domain by a peptide linker. The first and second binding domains can simultaneously bind to a single HIV-1 Env trimer, to synergistically neutralize HIV-1. Also disclosed are single-domain antibodies that specifically bind human immunodeficiency virus 1 (HIV-1) Envelope (Env) protein, wherein the single-domain antibody comprises the complementarity determining region 1 (CDR1), CDR2, and CDR3 sequences of SEQ ID NO: 1 (G36), SEQ ID NO: 5 (G36 K64E), SEQ ID NO: 7 (R27), or SEQ ID NO: 11 (R27 K64E). Also disclosed are compositions including the antibodies as well as related nucleic acid molecules and expression vectors. The disclosed bispecific and single domain antibodies potently neutralize HIV-1 in an accepted in vitro model of HIV-1 infection. Accordingly, a method is disclosed for inhibiting an HIV-1 infection in a subject, comprising administering an amount of one or more of the disclosed bispecific or single domain antibodies or nucleic acid molecules, vectors, or compositions, to the subject, effective to prevent or treat HIV-1 infection in the subject. In several implementations, the subject is at risk of or has an HIV-1 infection. The bispecific and single domain antibodies, nucleic acid molecules, vectors, and compositions provided herein can be used for a variety of additional purposes, such as for detecting an HIV-1 infection or diagnosing HIV-1 infection in a subject, or detecting HIV-1 in a sample.4239-111089-02The foregoing and other features and advantages of this disclosure will become more apparent from the following detailed description of several implementations which proceeds with reference to the accompanying figures. BRIEF DESCRIPTION OF THE FIGURES FIGs.1A-1D. BG505 DS-SOSIP immunized llama develops broadly neutralizing serum responses. FIG.1A: Llama immunization scheme. Llama was immunized with BG505 DS-SOSIP subcutaneously once every 21 days (except the last boost) as indicated above the arrow line, and serum was collected 10 days after each injection starting from day 52 as indicated beneath the arrow line. FIG.1B: Llama sera ELISA against different HIV Env probes. FIG.1C: Llama sera neutralization test on 14-strain panel. Color shading represents potency as indicated on the right of the table. FIG.1D: Dendrogram of the neutralization activity of day 188 and day 271 sera on a 60-strain panel. FIGs.2A-2F. Nanobodies from BG505 DS-SOSIP immunized llama target diverse regions on HIV-1 Env trimer. FIG.2A: Nanobody phage library construction and screening. Four probes used for phage screening are: Env Trimer (BG505 DS-SOSIP), Fusion peptide, Glycan base trimer (BG505 DS-SOSIP.4mut_N502-660) and RSC3. FIG.2B: Summary of epitope mapping of 151 nanobodies. FIGs.2C-2D: Summary of epitopes of 151 nanobodies from day 188 library.30 nanobodies selected for small panel neutralization test are grouped into 4 categories: Non-neutralizer (one line); Weak neutralizer (two lines); Moderate neutralizer (three lines); Broad neutralizer (four lines plus one red arrow). Control nanobody J3 is marked with four lines and one blue arrow. FIG.2E: 14-strain neutralization of 6 CD4bs-targeting nanobodies from day 188 library. FIG.2F: Neutralization of 17 unique nanobodies identified from day 271 library. FIGs.3A-3C. Nanobody neutralization from top three lineages. FIG.3A: Phylogenetic tree of three selected nanobody lineages.42 nanobodies from the three lineages were tested on a 10-strain panel first, then top 6 candidates (IC50<50 ug / ml) were further test on additional 15-strain panel. Neutralization breadth of the the top 6 nanobodies on 25-strain panel was shown beneath nanobody names. FIG.3B: 10-strain neutralization of 42 nanobodies from the three selected lineages. FIG.3C: 25-strain neutralization of 6 selected nanobodies from panel B. The broadest (G36) and most potent (R27) nanobodies were selected for further analysis.4239-111089-02FIGs.4A-4E. Immunization-elicited nanobodies, G36 and R27, in nanobody x3- IgG2a format, show broad and potent HIV-1 neutralization. FIG.4A: Scheme of nanobody forms. FIG.4B: 5-strain neutralization of nanobody monomers, bivalent and nanobody x3-IgG2a. FIG.4C: 25-strain neutralization of nanobodies. FIG.4D: 208-strain neutralization of G36x3-IgG2a and R27x3-IgG2a, IC50 shown is geometric mean. FIG.4E: Comparison of neutralization breadth and potency for G36x3-IgG2a and R27x3-IgG2a with other human antibodies and vaccine-elicited NHP antibodies on 208-strain panel. FIGs.5A-5G. Cryo-EM structures of nanobodies R27 and G36 in complex with HIV-1 Env trimer reveal modes of recognition similar to J3. FIG.5A: Cryo-EM structure of nanobody R27 in complex with HIV-1 BG505 DS-SOSIP Env. Overall cryo-EM density map and refined model are shown in two views with gp120 protomers colored green, cyan and slate, respectively. The density and model nanobody R27 are colored orange. The contour level of Cryo-EM map is 9.5 s. FIG.5B: Cryo-EM structure of VHH G36 in complex with HIV-1 BG505 DS-SOSIP Env. Overall cryo-EM density map and refined model are shown in two views with gp120 protomers colored green, cyan and slate, respectively. The density and model G36 are colored magenta. The contour level of Cryo-EM map is 9.6 s. FIG.5C: Epitopes of R27 and G36 on BG505 DS-SOSIP. Epitopes of R27, G36 and J3 are shown in orange, magenta and pink surfaces, respectively. R27 has much smaller contact area on the neighboring protomer. FIG.5D: Comparison of binding modes and angles. (Left) Structures of nanobodies R27, G36, and J3 are aligned with CD4 by the gp120 domain shown in green. R27, G36, and J3 are roughly in a similar position with N termini (labeled with “N”) in close proximity. (Right) The axes of R27, G36 and J3 are shown in orange, magenta and pink rods. Axes of CD4 domain1 and FV domain of VRC01 class antibody N6 are shown in yellow- and olive-colored rods for comparison. FIG.5E: Detailed interactions between nanobodies and BG505 DS-SOSIP. Residues that form hydrogen bonds and salt bridge are highlighted with sticks representation with bonds between atoms shown in gray dotted lines. Nanobodies and protomers of HIV Env are colored the same as in FIGs.5A-5B. FIG.5F: Alignment of nanobody sequences. Paratope residues are colored in orange and magenta, respectively. Residues interacting with neighboring protomer are colored in lighter shade. Residues interacting with both protomers are underlined. FIG.5G: Nanobody mimicry of CD4 Phe43 interaction with gp120. G36, like J3, inserts Tyr99 into the “Phe43 pocket” on gp120, whereas R27 has an Ala at this position.4239-111089-02FIGs.6A-6D. Ultra-potent HIV-1 bispecific antibodies from attaching nanobodies to the light chain of V2-apex-directed antibody CAP256V2LS. FIG.6A: Schematic of CAP256L-nanobody chimeras. FIG.6B: 38-strain neutralization of nanobodies. FIG.6C: Dendrogram of 80-strain panel neutralization. FIG.6D: Comparison of neutralization breadth and potency for R27 and G36 constructs with other potent antibodies on 208-strain panel. Data for CAP256L-G36x3LS and CAP256L-R27x3LS are estimates from 80-strain data in FIG.6C. Bispecific and trispecific antibodies are shown in star symbols. FIGs.7A-7B. Cryo-EM structure of CAP256L-R27LS Fab in complex with HIV- 1 Env reveals CAP256 and R27 to bind prefusion-closed trimer at Apex and CD4bs simultaneously. Cryo-EM density (FIG.7A) and refined model (FIG.7B) for the CAP256- R27-BG505 DS SOSIP complex were shown in two 90o-views and colored by chains. The chimera antibody bound to the HIV-1 Env with CAP256L CDR H3 (colored olive) inserted into the V2-apex and the CAP256LS light chain (skyblue)-linked R27 contacting one of the CD4-binding sites, however, the density of the flexible linker between R27 and CAP256L light chain was disordered. Three copies of R27 were observed to bind to each of the 3 CD4bs on the HIV-1 Env, indicating the other two R27 were from different chimera antibodies. FIGs.8A-8C. CAP256L-R27x3LS autoreactivity and half-life in human FcRn-Fc KI mice. FIG.8A: Autoreactivity of antibodies determined by HEp-2 cell binding assay. FIG.8B: Summary of autoreactivity of antibodies determined by by HEp-2 cell binding assay and anti-Cardiolipin ELISA assay. FIG.8C: In vivo half-life of CAP256L-nanobody variants assessed in a human FcRn-Fc knock-in mouse model. FIGs.9A-9B. Serum neutralization response in BG505 DS-SOSIP immunized llama. FIG.9A: 60-strain serum neutralization. FIG.9B: Neutralization fingerprinting of day 188 and day 271 serum samples. FIGs.10A-10C. Screening of HIV-1 neutralizing nanobodies from day 188 and day 271 libraries. FIG.10A: Epitope mapping of 16 nanobodies from day 188 library. FIG. 10B: Neutralization of 24 non-CD4bs targeting nanobodies. FIG.10C: Alignment of day 271 nanobodies with selected day 181 nanobodies. The sequences of the following are shown: D188_G36 (SEQ ID NO: 1), D271_G1 (SEQ ID NO: 58), D188_R21 (SEQ ID NO: 59), D188_R25 (SEQ ID NO: 60), D188_R18 (SEQ ID NO: 61), D188_G42 (SEQ ID NO: 62), D188_R11 (SEQ ID NO: 63), D271_R27 (SEQ ID NO: 7), D271_E46 (SEQ ID NO: 64), D271_E3 (SEQ ID NO: 65), D271_G13 (SEQ ID NO: 66), D271_G48 (SEQ ID NO: 67),4239-111089-02D271_G43 (SEQ ID NO: 68), D271_E12 (SEQ ID NO: 69), D271_G33 (SEQ ID NO: 70), D271_G37 (SEQ ID NO: 71), D271_E34 (SEQ ID NO: 72), D271_E4 (SEQ ID NO: 73), D271_E39 (SEQ ID NO: 74), D271_E14 (SEQ ID NO: 75), D271_E58 (SEQ ID NO: 76), D271_G9 (SEQ ID NO: 77), and D271_E24 (SEQ ID NO: 78). FIGs.11A-11C. Improve neutralization potency and breadth by Fc conjugation and multimerization. FIG.11A: 5-strain neutralization of nanobody monomers, bivalent and nanobody x3-IgG2a. FIG.11B: 25-strain neutralization of engineered nanobodies. FIG.11C: IC80 of 208-strain neutralization. FIGs.12A-12E. Cryo-EM details of R27 in complex with BG505 DS-SOSIP. FIG. 12A: Representative micrograph. FIG.12B: Representative 2D class averages are shown. FIG.12C The gold-standard Fourier shell correlation resulted in a resolution of 3.58 Å for the overall map using non-uniform refinement with C1 symmetry (top panel); the orientations of all particles used in the final refinement are shown as a heatmap (bottom panel). FIG.12D: The local resolution of the final overall map is shown contoured at 0.809 (9.5 s). Resolution estimation was generated through cryoSPARC using an FSC cutoff of 0.5. FIG.12E: Representative cryo-EM density for the CDR H3 region. The contour level is 6 s. FIGs.13A-13E. Cryo-EM details of G36 in complex with BG505 DS-SOSIP. FIG. 13A: Representative micrograph. FIG.13B: Representative 2D class averages are shown. FIG.13C: The gold-standard Fourier shell correlation resulted in a resolution of 3.32 Å for the overall map using non-uniform refinement with C1 symmetry (top panel); the orientations of all particles used in the final refinement are shown as a heatmap (bottom panel). FIG.13D: The local resolution of the final overall map is shown contoured at 0.956 (9.6 s). Resolution estimation was generated through cryoSPARC using an FSC cutoff of 0.5. FIG.13E: Representative cryo-EM density for the CDR H3 region. The contour level is 5 s. FIGs.14A-14F. Cryo-EM details of CAP256L-R27LS Fab in complex with BG505 DS-SOSIP. FIG.14A: Representative micrograph. FIG.14B: Representative 2D class averages are shown. FIG.14C: The gold-standard Fourier shell correlation resulted in a resolution of 3.61 Å for the overall map using non-uniform refinement with C1 symmetry (top panel); the orientations of all particles used in the final refinement are shown as a heatmap (bottom panel). FIG.14D: The local resolution of the final overall map is shown contoured at 0.33 (8.1 s). Resolution estimation was generated through cryoSPARC using an FSC cutoff of 0.5. FIG.14E: Representative cryo-EM density of CAP256 CDR H3 region. The contour level is 4.5 s. FIG.14F: Cryo-EM density of the CAP256L-R27-BG505 DS SOSIP complex at low contour (2.5 s) showing extra disordered density connecting to two4239-111089-02R27s, indicating these two R27s were from separate CAP256L-R27 molecules. The density was colored the same as in FIG.7A-7B with un-modeled density colored gray. FIGs.15A-15C. Binding surfaces and bonds in the R27-BG505 DS-SOSIP complex. FIG.15A: Binding surface areas at the interface of R27 and BG505 DS-SOSIP. R27 contacts two neighboring protomers in the trimeric HIV-1 Env. Listed is data analysis for one R27 (chain J) with its major binding gp120 (chain A) and minor binding gp120 (chain E). FIG.15B: Hydrogen bonds between R27 and gp120. FIG.15C: Interface residues and their contributions. FIGs.16A-16C. Binding surfaces and bonds in the G36-BG505 DS-SOSIP complex. FIG.16A: Binding surface areas at the interface of nanobody G36 and BG505 DS- SOSIP. G36 contacts two neighboring protomers in the trimeric HIV-1 Env. Listed is data analysis for one G36 (chain J) with its major binding gp120 (chain A) and minor binding gp120 (chain E). FIG.16B: Hydrogen bonds between G36 and gp120. FIG.16C: Interface residues and their contributions. Listed is data analysis for one G36 (chain J) with its major binding gp120 (chain A) and minor binding gp120 (chain E). * Glycan 197 interaction data is from chain H and gp120 (chain C) with showed better cryo-EM density for this region. FIGs.17A-17B. Estimation of 208-strain neutralization of CAP256L-G36x3LS and CAP256L-R27x3LS. FIGs.17A: Estimated IC50 of CAP256L-G36x3LS and CAP256L-R27x3LS. FIG.17B: IC80 comparison of the two bispecific antibodies with two reference antibodies. FIG.18. Cryo-EM Data Collection, Refinement and Validation Statistics for R27, G36 and CAP256L-R27 in complex with HIV-1 BG505 DS-SOSIP. SEQUENCES The nucleic and amino acid sequences listed herein are shown using standard letter abbreviations for nucleotide bases, and single letter code for amino acids, as defined in 37 C.F.R.1.822. Only one strand of each nucleic acid sequence is shown, but the complementary strand is understood as included by any reference to the displayed strand. SEQ ID NO: 1 is the amino acid sequence of the G36 VHH. QVQLQESGGGSVQPGGSLRLSCAVSGLDVESVTIGWIRQAPGKEREEVGCISGNFDQTYYVD SVKGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS S4239-111089-02SEQ ID NOs: 2-4 are the CDR sequences of the G36 VHH. SEQ ID NO: 2 – HCDR1, SVTIG SEQ ID NO: 3 – HCDR2, CISGNFDQTYYVDSVKG SEQ ID NO: 4 – HCDR3, VTDRQFYCALHRLPVS SEQ ID NO: 5 is the amino acid sequence of the G36 K64E VHH. QVQLQESGGGSVQPGGSLRLSCAVSGLDVESVTIGWIRQAPGKEREEVGCISGNFDQTYYVD SVEGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS S SEQ ID NOs: 6 is the CDR sequence of the CD2 of G36 K64E VHH. SEQ ID NO: 6 – HCDR2, CISGNFDQTYYVDSVEG SEQ ID NO: 7 is the amino acid sequence of the R27 VHH. QVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFRQAPGKAREGVACLSKNSGIGHSVK GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSS SEQ ID NOs: 8-10 are the CDR sequences of the R27 VHH. SEQ ID NO: 8 – HCDR1, NYSIG SEQ ID NO: 9 – HCDR2, CLSKNSGIGHSVKG SEQ ID NO: 10 – HCDR3, ATYNRACANYVTIWP SEQ ID NO: 11 is the amino acid sequence of the R27 K64E VHH. QVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFRQAPGKAREGVACLSKNSGIGHSVE GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSS SEQ ID NOs: 12 is the CDR sequence of the CDR2 of R27 K64E VHH. SEQ ID NO: 12 – HCDR2, CLSKNSGIGHSVEG SEQ ID NO: 13 is the amino acid sequence of the G36 R19E VHH. QVQLQESGGGSVQPGGSLELSCAVSGLDVESVTIGWIRQAPGKEREEVGCISGNFDQTYYVD SVKGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS S SEQ ID NO: 14 is the amino acid sequence of the G36 R19E K43E K64E VHH. QVQLQESGGGSVQPGGSLELSCAVSGLDVESVTIGWIRQAPGEEREEVGCISGNFDQTYYVD SVEGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS S4239-111089-02SEQ ID NO: 15 is the amino acid sequence of the R27 R19E VHH. QVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFRQAPGKAREGVACLSKNSGIGHSVK GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSS SEQ ID NO: 16 is the amino acid sequence of the R27 R19E K43E K64E VHH. QVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFRQAPGEAREGVACLSKNSGIGHSVE GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSS SEQ ID NO: 17 is the amino acid sequence of the G36x3 VHH trimer. QVQLQESGGGSVQPGGSLRLSCAVSGLDVESVTIGWIRQAPGKEREEVGCISGNFDQTYYVD SVKGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS SGGGGSGGGGSGGGGSQVQLQESGGGSVQPGGSLRLSCAVSGLDVESVTIGWIRQAPGKERE EVGCISGNFDQTYYVDSVKGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHR LPVSQYRGQGTQVTVSSGGGGSGGGGSGGGGSQVQLQESGGGSVQPGGSLRLSCAVSGLDVE SVTIGWIRQAPGKEREEVGCISGNFDQTYYVDSVKGRFTISRVNEENTVYLQMDNLKPEDTA TYYCVTDRQFYCALHRLPVSQYRGQGTQVTVSS SEQ ID NO: 18 is the amino acid sequence of the G36x3 R19E VHH trimer. QVQLQESGGGSVQPGGSLELSCAVSGLDVESVTIGWIRQAPGKEREEVGCISGNFDQTYYVD SVKGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS SggggsggggsggggsQVQLQESGGGSVQPGGSLELSCAVSGLDVESVTIGWIRQAPGKERE EVGCISGNFDQTYYVDSVKGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHR LPVSQYRGQGTQVTVSSggggsggggsggggsQVQLQESGGGSVQPGGSLELSCAVSGLDVE SVTIGWIRQAPGKEREEVGCISGNFDQTYYVDSVKGRFTISRVNEENTVYLQMDNLKPEDTA TYYCVTDRQFYCALHRLPVSQYRGQGTQVTVSS SEQ ID NO: 19 is the amino acid sequence of the G36x3 K64E VHH trimer. QVQLQESGGGSVQPGGSLRLSCAVSGLDVESVTIGWIRQAPGKEREEVGCISGNFDQTYYVD SVEGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS SggggsggggsggggsQVQLQESGGGSVQPGGSLRLSCAVSGLDVESVTIGWIRQAPGKERE EVGCISGNFDQTYYVDSVEGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHR LPVSQYRGQGTQVTVSSggggsggggsggggsQVQLQESGGGSVQPGGSLRLSCAVSGLDVE SVTIGWIRQAPGKEREEVGCISGNFDQTYYVDSVEGRFTISRVNEENTVYLQMDNLKPEDTA TYYCVTDRQFYCALHRLPVSQYRGQGTQVTVSS SEQ ID NO: 20 is the amino acid sequence of the G36x3 R19E K43E K64E VHH trimer. QVQLQESGGGSVQPGGSLELSCAVSGLDVESVTIGWIRQAPGEEREEVGCISGNFDQTYYVD SVEGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS SggggsggggsggggsQVQLQESGGGSVQPGGSLELSCAVSGLDVESVTIGWIRQAPGEERE EVGCISGNFDQTYYVDSVEGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHR LPVSQYRGQGTQVTVSSggggsggggsggggsQVQLQESGGGSVQPGGSLELSCAVSGLDVE SVTIGWIRQAPGEEREEVGCISGNFDQTYYVDSVEGRFTISRVNEENTVYLQMDNLKPEDTA TYYCVTDRQFYCALHRLPVSQYRGQGTQVTVSS4239-111089-02SEQ ID NO: 21 is the amino acid sequence of the R27x3 VHH trimer. QVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFRQAPGKAREGVACLSKNSGIGHSVK GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSSGGG GSGGGGSGGGGSQVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFRQAPGKAREGVAC LSKNSGIGHSVKGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRG QGTQVTVSSGGGGSGGGGSGGGGSQVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFR QAPGKAREGVACLSKNSGIGHSVKGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRAC ANYVTIWPEFRGQGTQVTVSS SEQ ID NO: 22 is the amino acid sequence of the R27x3 R19E VHH trimer. QVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFRQAPGKAREGVACLSKNSGIGHSVK GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSSggg gsggggsggggsQVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFRQAPGKAREGVAC LSKNSGIGHSVKGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRG QGTQVTVSSggggsggggsggggsQVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFR QAPGKAREGVACLSKNSGIGHSVKGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRAC ANYVTIWPEFRGQGTQVTVSS SEQ ID NO: 23 is the amino acid sequence of the R27x3 K64E VHH trimer. QVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFRQAPGKAREGVACLSKNSGIGHSVE GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSSggg gsggggsggggsQVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFRQAPGKAREGVAC LSKNSGIGHSVEGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRG QGTQVTVSSggggsggggsggggsQVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFR QAPGKAREGVACLSKNSGIGHSVEGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRAC ANYVTIWPEFRGQGTQVTVSS SEQ ID NO: 24 is the amino acid sequence of the R27x3 R19E K43E K64E VHH trimer. QVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFRQAPGEAREGVACLSKNSGIGHSVE GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSSggg gsggggsggggsQVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFRQAPGEAREGVAC LSKNSGIGHSVEGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRG QGTQVTVSSggggsggggsggggsQVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFR QAPGEAREGVACLSKNSGIGHSVEGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRAC ANYVTIWPEFRGQGTQVTVSS SEQ ID NO: 25 is the amino acid sequence of the CAP256V2LS VH. QVQLVESGGGVVQPGTSLRLSCAASQFRFDGYGMHWVRQAPGKGLEWVASISHDGIKKYHAE KVWGRFTISRDNSKNTLYLQMNSLRPEDTALYYCAKDLREDECEEWWSDYYDFGAQLPCAKS RGGLVGIADNWGQGTMVTVSS SEQ ID NOs: 26-28 are the CDR sequences of the CAP256V2LS VH. SEQ ID NO: 26 – HCDR1, GYGMH SEQ ID NO: 27– HCDR2, SISHDGIKKYHAEKVW4239-111089-02SEQ ID NO: 28 – HCDR3, DLREDECEEWWSDYYDFGAQLPCAKSRGGLVGIADN SEQ ID NO: 29 is the amino acid sequence of the CAP256V2LS VL. QSVLTQPPSVSAAPGQKVTISCSGNTSNIGNNFVSWYQQRPGRAPQLLIYETDKRPSGIPDR FSASKSGTSGTLAITGLQTGDEADYYCATWAASLSSARVFGTGTQVIVL SEQ ID NOs: 30-32 are the CDR sequences of the CAP256V2LS VL. SEQ ID NO: 30 – LCDR1, SGNTSNIGNNFVS SEQ ID NO: 31 – LCDR2, ETDKRPS SEQ ID NO: 32 – LCDR3, ATWAASLSSARV SEQ ID NO: 33 is the amino acid sequence of the VRC26.25 light chain fused to G36 VHH. QVQLQESGGGSVQPGGSLRLSCAVSGLDVESVTIGWIRQAPGKEREEVGCISGNFDQTYYVD SVKGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS SggsggggsggggsggQSVLTQPPSVSAAPGQKVTISCSGNTSNIGNNFVSWYQQRPGRAPQ LLIYETDKRPSGIPDRFSASKSGTSGTLAITGLQTGDEADYYCATWAASLSSARVFGTGTQV IVLGQPKVNPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPS KQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO: 34 is the amino acid sequence of the VRC26.25 light chain fused to G36 R19E, K43E, K64E VHH QVQLQESGGGSVQPGGSLELSCAVSGLDVESVTIGWIRQAPGEEREEVGCISGNFDQTYYVD SVEGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS SggsggggsggggsggQSVLTQPPSVSAAPGQKVTISCSGNTSNIGNNFVSWYQQRPGRAPQ LLIYETDKRPSGIPDRFSASKSGTSGTLAITGLQTGDEADYYCATWAASLSSARVFGTGTQV IVLGQPKVNPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPS KQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO: 35 is the amino acid sequence of the VRC26.25 light chain fused to G36 VHH trimer. QVQLQESGGGSVQPGGSLRLSCAVSGLDVESVTIGWIRQAPGKEREEVGCISGNFDQTYYVD SVKGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS SggggsggggsggggsQVQLQESGGGSVQPGGSLRLSCAVSGLDVESVTIGWIRQAPGKERE EVGCISGNFDQTYYVDSVKGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHR LPVSQYRGQGTQVTVSSggggsggggsggggsQVQLQESGGGSVQPGGSLRLSCAVSGLDVE SVTIGWIRQAPGKEREEVGCISGNFDQTYYVDSVKGRFTISRVNEENTVYLQMDNLKPEDTA TYYCVTDRQFYCALHRLPVSQYRGQGTQVTVSSggsggggsggggsggQSVLTQPPSVSAAP GQKVTISCSGNTSNIGNNFVSWYQQRPGRAPQLLIYETDKRPSGIPDRFSASKSGTSGTLAI TGLQTGDEADYYCATWAASLSSARVFGTGTQVIVLGQPKVNPTVTLFPPSSEELQANKATLV CLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQV THEGSTVEKTVAPTECS4239-111089-02SEQ ID NO: 36 is the amino acid sequence of the VRC26.25 light chain fused to G36 R19E VHH trimer. QVQLQESGGGSVQPGGSLELSCAVSGLDVESVTIGWIRQAPGKEREEVGCISGNFDQTYYVD SVKGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS SggggsggggsggggsQVQLQESGGGSVQPGGSLELSCAVSGLDVESVTIGWIRQAPGKERE EVGCISGNFDQTYYVDSVKGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHR LPVSQYRGQGTQVTVSSggggsggggsggggsQVQLQESGGGSVQPGGSLELSCAVSGLDVE SVTIGWIRQAPGKEREEVGCISGNFDQTYYVDSVKGRFTISRVNEENTVYLQMDNLKPEDTA TYYCVTDRQFYCALHRLPVSQYRGQGTQVTVSSggsggggsggggsggQSVLTQPPSVSAAP GQKVTISCSGNTSNIGNNFVSWYQQRPGRAPQLLIYETDKRPSGIPDRFSASKSGTSGTLAI TGLQTGDEADYYCATWAASLSSARVFGTGTQVIVLGQPKVNPTVTLFPPSSEELQANKATLV CLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQV THEGSTVEKTVAPTECS SEQ ID NO: 37 is the amino acid sequence of the VRC26.25 light chain fused to G36 R19E, K43E, K64E VHH trimer. QVQLQESGGGSVQPGGSLELSCAVSGLDVESVTIGWIRQAPGEEREEVGCISGNFDQTYYVD SVEGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS SggggsggggsggggsQVQLQESGGGSVQPGGSLELSCAVSGLDVESVTIGWIRQAPGEERE EVGCISGNFDQTYYVDSVEGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHR LPVSQYRGQGTQVTVSSggggsggggsggggsQVQLQESGGGSVQPGGSLELSCAVSGLDVE SVTIGWIRQAPGEEREEVGCISGNFDQTYYVDSVEGRFTISRVNEENTVYLQMDNLKPEDTA TYYCVTDRQFYCALHRLPVSQYRGQGTQVTVSSggsggggsggggsggQSVLTQPPSVSAAP GQKVTISCSGNTSNIGNNFVSWYQQRPGRAPQLLIYETDKRPSGIPDRFSASKSGTSGTLAI TGLQTGDEADYYCATWAASLSSARVFGTGTQVIVLGQPKVNPTVTLFPPSSEELQANKATLV CLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQV THEGSTVEKTVAPTECS SEQ ID NO: 38 is the amino acid sequence of the VRC26.25 light chain fused to R27 VHH. QVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFRQAPGKAREGVACLSKNSGIGHSVK GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSSggs ggggsggggsggQSVLTQPPSVSAAPGQKVTISCSGNTSNIGNNFVSWYQQRPGRAPQLLIY ETDKRPSGIPDRFSASKSGTSGTLAITGLQTGDEADYYCATWAASLSSARVFGTGTQVIVLG QPKVNPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSN NKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS SEQ ID NO: 39 is the amino acid sequence of the VRC26.25 light chain fused to R27 R19E, K43E, K64E VHH QVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFRQAPGEAREGVACLSKNSGIGHSVE GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSSggs ggggsggggsggQSVLTQPPSVSAAPGQKVTISCSGNTSNIGNNFVSWYQQRPGRAPQLLIY ETDKRPSGIPDRFSASKSGTSGTLAITGLQTGDEADYYCATWAASLSSARVFGTGTQVIVLG QPKVNPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSN NKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS4239-111089-02SEQ ID NO: 40 is the amino acid sequence of the VRC26.25 light chain fused to R27 VHH trimer. QVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFRQAPGKAREGVACLSKNSGIGHSVK GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSSggg gsggggsggggsQVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFRQAPGKAREGVAC LSKNSGIGHSVKGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRG QGTQVTVSSggggsggggsggggsQVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFR QAPGKAREGVACLSKNSGIGHSVKGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRAC ANYVTIWPEFRGQGTQVTVSSggsggggsggggsggQSVLTQPPSVSAAPGQKVTISCSGNT SNIGNNFVSWYQQRPGRAPQLLIYETDKRPSGIPDRFSASKSGTSGTLAITGLQTGDEADYY CATWAASLSSARVFGTGTQVIVLGQPKVNPTVTLFPPSSEELQANKATLVCLISDFYPGAVT VAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVA PTECS SEQ ID NO: 41 is the amino acid sequence of the VRC26.25 light chain fused to R27 R19E VHH trimer. QVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFRQAPGKAREGVACLSKNSGIGHSVK GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSSggg gsggggsggggsQVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFRQAPGKAREGVAC LSKNSGIGHSVKGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRG QGTQVTVSSggggsggggsggggsQVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFR QAPGKAREGVACLSKNSGIGHSVKGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRAC ANYVTIWPEFRGQGTQVTVSSggsggggsggggsggQSVLTQPPSVSAAPGQKVTISCSGNT SNIGNNFVSWYQQRPGRAPQLLIYETDKRPSGIPDRFSASKSGTSGTLAITGLQTGDEADYY CATWAASLSSARVFGTGTQVIVLGQPKVNPTVTLFPPSSEELQANKATLVCLISDFYPGAVT VAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVA PTECS SEQ ID NO: 42 is the amino acid sequence of the VRC26.25 light chain fused to R27 R19E, K43E, K64E VHH trimer. QVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFRQAPGEAREGVACLSKNSGIGHSVE GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSSggg gsggggsggggsQVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFRQAPGEAREGVAC LSKNSGIGHSVEGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRG QGTQVTVSSggggsggggsggggsQVQLQESGGGLVQPGGSLELSCVASGFDLENYSIGWFR QAPGEAREGVACLSKNSGIGHSVEGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRAC ANYVTIWPEFRGQGTQVTVSSggsggggsggggsggQSVLTQPPSVSAAPGQKVTISCSGNT SNIGNNFVSWYQQRPGRAPQLLIYETDKRPSGIPDRFSASKSGTSGTLAITGLQTGDEADYY CATWAASLSSARVFGTGTQVIVLGQPKVNPTVTLFPPSSEELQANKATLVCLISDFYPGAVT VAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVA PTECS SEQ ID NO: 43 is the amino acid sequence of a peptide linker. GGSGGGGSGGGGSGG SEQ ID NOs: 44-48 are the amino acid sequences of peptide linkers.4239-111089-02SEQ ID NO: 49 is the amino acid sequence of the VRC26.25 light chain fused to G36 K64E VHH trimer. QVQLQESGGGSVQPGGSLRLSCAVSGLDVESVTIGWIRQAPGKEREEVGCISGNFDQTYYVD SVEGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS SggggsggggsggggsQVQLQESGGGSVQPGGSLRLSCAVSGLDVESVTIGWIRQAPGKERE EVGCISGNFDQTYYVDSVEGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHR LPVSQYRGQGTQVTVSSggggsggggsggggsQVQLQESGGGSVQPGGSLRLSCAVSGLDVE SVTIGWIRQAPGKEREEVGCISGNFDQTYYVDSVEGRFTISRVNEENTVYLQMDNLKPEDTA TYYCVTDRQFYCALHRLPVSQYRGQGTQVTVSSggsggggsggggsggQSVLTQPPSVSAAP GQKVTISCSGNTSNIGNNFVSWYQQRPGRAPQLLIYETDKRPSGIPDRFSASKSGTSGTLAI TGLQTGDEADYYCATWAASLSSARVFGTGTQVIVLGQPKVNPTVTLFPPSSEELQANKATLV CLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQV THEGSTVEKTVAPTECS SEQ ID NO: 50 is the amino acid sequence of the VRC26.25 light chain fused to R27 K64E VHH trimer. QVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFRQAPGKAREGVACLSKNSGIGHSVE GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSSggg gsggggsggggsQVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFRQAPGKAREGVAC LSKNSGIGHSVEGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRG QGTQVTVSSggggsggggsggggsQVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFR QAPGKAREGVACLSKNSGIGHSVEGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRAC ANYVTIWPEFRGQGTQVTVSSggsggggsggggsggQSVLTQPPSVSAAPGQKVTISCSGNT SNIGNNFVSWYQQRPGRAPQLLIYETDKRPSGIPDRFSASKSGTSGTLAITGLQTGDEADYY CATWAASLSSARVFGTGTQVIVLGQPKVNPTVTLFPPSSEELQANKATLVCLISDFYPGAVT VAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVA PTECS SEQ ID NO: 51 is the amino acid sequence of a IgG2a Fc region AAAEPKIPQPQPKPQPQPQPQPKPQPKPEPECTCPKCPAPELLGGPSVFLFPPKPKDTLMIS RTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGKLEVLFQGP SEQ ID NO: 52 is the amino acid sequence of G36x3-IgG2a QVQLQESGGGSVQPGGSLRLSCAVSGLDVESVTIGWIRQAPGKEREEVGCISGNFDQTYYVD SVKGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHRLPVSQYRGQGTQVTVS SGGGGSGGGGSGGGGSQVQLQESGGGSVQPGGSLRLSCAVSGLDVESVTIGWIRQAPGKERE EVGCISGNFDQTYYVDSVKGRFTISRVNEENTVYLQMDNLKPEDTATYYCVTDRQFYCALHR LPVSQYRGQGTQVTVSSGGGGSGGGGSGGGGSQVQLQESGGGSVQPGGSLRLSCAVSGLDVE SVTIGWIRQAPGKEREEVGCISGNFDQTYYVDSVKGRFTISRVNEENTVYLQMDNLKPEDTA TYYCVTDRQFYCALHRLPVSQYRGQGTQVTVSSAAAEPKIPQPQPKPQPQPQPQPKPQPKPE PECTCPKCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ4239-111089-02VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKLEVLFQGP SEQ ID NO: 53 is the amino acid sequence of R27x3-IgG2a QVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFRQAPGKAREGVACLSKNSGIGHSVK GRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRGQGTQVTVSSGGG GSGGGGSGGGGSQVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFRQAPGKAREGVAC LSKNSGIGHSVKGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRACANYVTIWPEFRG QGTQVTVSSGGGGSGGGGSGGGGSQVQLQESGGGLVQPGGSLRLSCVASGFDLENYSIGWFR QAPGKAREGVACLSKNSGIGHSVKGRFTISRDGDSNTWFLQMGALEAEDTAVYTCATYNRAC ANYVTIWPEFRGQGTQVTVSSAAAEPKIPQPQPKPQPQPQPQPKPQPKPEPECTCPKCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY NSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGKLEVLFQGP SEQ ID NO: 54 is the amino acid sequence ofHV3S61*01 QVQLVESGGGLVQPGGSLRLSCAASGFTLDYYAIGWFRQAPGKEREGVSCISSSDGSTYYAD SVEGRFTISRDDDKNTVYLQMNSLKPEGTAVYYC SEQ ID NO: 55 is the amino acid sequence of the R25 VHH QVQLQESGGGLVQPGGSLRLSCAASEDSLEDYAIGWFRQAPGKEHEGVACITGSVGNTHYAD FVEGRFTISRDDDKNTVYLEMNSLKPEDTALYYCAIQRFGCANWRTFYVDSMGKGTQVTVSS SEQ ID NO: 56 is the amino acid sequence ofHV3-3*01 QVQLVESGGGLVQAGGSLRLSCAASGRTFSSYAMGWFRQAPGKEREFVAAISWSGGSTYYADSVKGFT ISRDNAK SEQ ID NO: 57 is the amino acid sequence of the J3 VHH EVQLVESGGGLVQAGGFLRLSCELRGSIFNQYAMAWFRQAPGKEREFVAGMGAVPHYGEFVKGRFTIS RDNAKSTVYLQMSSLKPEDTAIYFCARSKSTYISYNSNGYDYWGRGTQVTVSS SEQ ID NOs: 58-78 are VHH amino acid sequences. In some implementations, several of the above sequences are used in the disclosed bispecific antibodies, for example as listed in the following table: Bispecific antibody Light chain fused to VHH Heavy chain ) 4239-111089-02CAP256-G36 VRC26.25L-G36 R19E+K43E+R64E CAP256V2LS H R19E+K43E+R64E (SEQ ID NO: 34) (SEQ ID NO: 25) AP2 VR 2 2 L AP2 V2L H ) ) ) ) ) ) ) ) ) ) I. Summary of Terms Unless otherwise noted, technical terms are used according to conventional usage. Definitions of many common terms in molecular biology may be found in Krebs et al. (eds.), Lewin’s genes XII, published by Jones & Bartlett Learning, 2017. As used herein, the singular forms “a,” “an,” and “the,” refer to both the singular as well as plural, unless the context clearly indicates otherwise. For example, the term “an antigen” includes singular or plural antigens and can be considered equivalent to the phrase “at least one antigen.” As used herein, the term “comprises” means “includes.” It is further to be understood that any and all base sizes or amino acid sizes, and all molecular weight or molecular mass values, given for nucleic acids or polypeptides are approximate, and are provided for descriptive purposes, unless otherwise indicated. Although many methods and materials similar or equivalent to those described herein can be used, particular suitable methods and materials are described herein. In case of conflict, the present specification, including explanations of terms, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. To facilitate review of the various implementations, the following explanations of terms are provided:4239-111089-02About: Unless context indicated otherwise, “about” refers to plus or minus 5% of a reference value. For example, “about” 100 refers to 95 to 105. Administration: The introduction of an agent, such as a disclosed antibody, into a subject by a chosen route. Administration can be local or systemic. For example, if the chosen route is intravascular, the agent (such as antibody) is administered by introducing the agent into a blood vessel of the subject. Exemplary routes of administration include, but are not limited to, oral, injection (such as subcutaneous, intramuscular, intradermal, intraperitoneal, and intravenous), sublingual, rectal, transdermal (for example, topical), intranasal, vaginal, and inhalation routes. Amino acid substitution: The replacement of one amino acid in a polypeptide with a different amino acid. Antibody and Antigen Binding Fragment: An immunoglobulin, antigen-binding fragment, or derivative thereof, that specifically binds and recognizes an analyte (antigen) such as HIV-1 Env. The term “antibody” is used herein in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antigen binding fragments, so long as they exhibit the desired antigen-binding activity. Non-limiting examples of antibodies include, for example, intact immunoglobulins and variants and fragments thereof that retain binding affinity for the antigen. Examples of antigen binding fragments include but are not limited to Fv, Fab, Fab', Fab'-SH, F(ab')2; diabodies; linear antibodies; single-chain antibody molecules (e.g. scFv); and multispecific antibodies formed from antibody fragments. Antibody fragments include antigen binding fragments either produced by the modification of whole antibodies or those synthesized de novo using recombinant DNA methodologies (see, e.g., Kontermann and Dübel (Eds.), Antibody Engineering, Vols.1-2, 2nded., Springer-Verlag, 2010). Antibodies also include genetically engineered forms such as chimeric antibodies (such as humanized murine antibodies) and heteroconjugate antibodies (such as bispecific antibodies). An antibody may have one or more binding sites. If there is more than one binding site, the binding sites may be identical to one another or may be different. For instance, a naturally-occurring immunoglobulin has two identical binding sites, a single-chain antibody or Fab fragment has one binding site, while a bispecific or bifunctional antibody has two different binding sites.4239-111089-02Typically, a naturally occurring immunoglobulin has heavy (H) chains and light (L) chains interconnected by disulfide bonds. Immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon and mu constant region genes, as well as the myriad immunoglobulin variable domain genes. There are two types of light chain, lambda (λ) and kappa (κ). There are five main heavy chain classes (or isotypes) which determine the functional activity of an antibody molecule: IgM, IgD, IgG, IgA and IgE. Each heavy and light chain contains a constant region (or constant domain) and a variable region (or variable domain). In combination, the heavy and the light chain variable regions specifically bind the antigen. References to “VH” or “VH” refer to the variable region of an antibody heavy chain, including that of an antigen binding fragment, such as Fv, scFv, dsFv or Fab. References to “VL” or “VL” refer to the variable domain of an antibody light chain, including that of an Fv, scFv, dsFv or Fab. The VHand VLcontain a “framework” region interrupted by three hypervariable regions, also called “complementarity-determining regions” or “CDRs” (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5thed., NIH Publication No.91-3242, Public Health Service, National Institutes of Health, U.S. Department of Health and Human Services, 1991). The sequences of the framework regions of different light or heavy chains are relatively conserved within a species. The framework region of an antibody, that is the combined framework regions of the constituent light and heavy chains, serves to position and align the CDRs in three-dimensional space. The CDRs are primarily responsible for binding to an epitope of an antigen. The amino acid sequence boundaries of a given CDR can be readily determined using any of a number of well-known schemes, including those described by Kabat et al. (Sequences of Proteins of Immunological Interest, 5thed., NIH Publication No.91-3242, Public Health Service, National Institutes of Health, U.S. Department of Health and Human Services, 1991; “Kabat” numbering scheme), Al-Lazikani et al., (“Standard conformations for the canonical structures of immunoglobulins,” J. Mol. Bio., 273(4):927-948, 1997; “Chothia” numbering scheme), and Lefranc et al. (“IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains,” Dev. Comp. Immunol., 27(1):55-77, 2003; “IMGT” numbering scheme). The CDRs of each chain are typically referred to as CDR1, CDR2, and CDR3 (from the N-terminus to C-terminus), and are also typically identified by the chain in which the particular CDR is located. Thus, a VH CDR3 is4239-111089-02the CDR3 from the VHof the antibody in which it is found, whereas a VLCDR1 is the CDR1 from the VLof the antibody in which it is found. Light chain CDRs are sometimes referred to as LCDR1, LCDR2, and LCDR3. Heavy chain CDRs are sometimes referred to as HCDR1, HCDR2, and HCDR3. In some implementations, a disclosed antibody includes a heterologous constant domain. For example, the antibody includes a constant domain that is different from a native constant domain, such as a constant domain including one or more modifications (such as the “LS” mutation) to increase half-life. A “monoclonal antibody” is an antibody obtained from a population of substantially homogeneous antibodies, that is, the individual antibodies comprising the population are identical and / or bind the same epitope, except for possible variant antibodies, for example, containing naturally occurring mutations or arising during production of a monoclonal antibody preparation, such variants generally being present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen. Thus, the modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies may be made by a variety of techniques, including but not limited to the hybridoma method, recombinant DNA methods, phage-display methods, and methods utilizing transgenic animals containing all or part of the human immunoglobulin loci, such methods and other exemplary methods for making monoclonal antibodies being described herein. In some examples monoclonal antibodies are isolated from a subject. Monoclonal antibodies can have conservative amino acid substitutions which have substantially no effect on antigen binding or other immunoglobulin functions. (See, for example, Greenfield (Ed.), Antibodies: A Laboratory Manual, 2nded. New York: Cold Spring Harbor Laboratory Press, 2014.) A “single-domain antibody” refers to an antibody having a single domain (a variable domain) that is capable of specifically binding an antigen, or an epitope of an antigen, in the absence of an additional antibody domain. Single-domain antibodies include, for example, camelid VHH antibodies, VNARantibodies, VHdomain antibodies and VLdomain antibodies. VNAR antibodies are produced by cartilaginous fish, such as nurse sharks, wobbegong sharks, spiny dogfish and bamboo sharks. Camelid VHH antibodies are produced by several species4239-111089-02including camel, llama, alpaca, dromedary, and guanaco, which produce heavy chain antibodies that are naturally devoid of light chains. A “humanized” antibody or antigen binding fragment includes a human framework region and one or more CDRs from a non-human (such as a mouse, rat, or synthetic) antibody or antigen binding fragment. The non-human antibody or antigen binding fragment providing the CDRs is termed a “donor,” and the human antibody or antigen binding fragment providing the framework is termed an “acceptor.” In one implementation, all the CDRs are from the donor immunoglobulin in a humanized immunoglobulin. Constant regions need not be present, but if they are, they can be substantially identical to human immunoglobulin constant regions, such as at least about 85-90%, such as about 95% or more identical. Hence, all parts of a humanized antibody or antigen binding fragment, except possibly the CDRs, are substantially identical to corresponding parts of natural human antibody sequences. A “chimeric antibody” is an antibody which includes sequences derived from two different antibodies, which typically are of different species. In some examples, a chimeric antibody includes one or more CDRs and / or framework regions from one human antibody and CDRs and / or framework regions from another human antibody. A “fully human antibody” or “human antibody” is an antibody which includes sequences from (or derived from) the human genome, and does not include sequence from another species. In some implementations, a human antibody includes CDRs, framework regions, and (if present) an Fc region from (or derived from) the human genome. Human antibodies can be identified and isolated using technologies for creating antibodies based on sequences derived from the human genome, for example by phage display or using transgenic animals (see, e.g., Barbas et al. Phage display: A Laboratory Manuel. 1stEd. New York: Cold Spring Harbor Laboratory Press, 2004. Print.; Lonberg, Nat. Biotech., 23: 1117-1125, 2005; Lonenberg, Curr. Opin. Immunol., 20:450-459, 2008). Biological sample: A sample obtained from a subject. Biological samples include all clinical samples useful for detection of disease or infection (for example, HIV-1 infection) in subjects, including, but not limited to, cells, tissues, and bodily fluids, such as blood, derivatives and fractions of blood (such as serum), cerebrospinal fluid; as well as biopsied or surgically removed tissue, for example tissues that are unfixed, frozen, or fixed in formalin or paraffin. In a particular example, a biological sample is obtained from a subject having or suspected of having an HIV-1 infection. Bispecific antibody that neutralizes HIV-1: A bispecific antibody that specifically binds to HIV-1 Env in such a way as to inhibit a biological function associated with HIV-14239-111089-02Env (such as binding to its target receptor). In several implementations, a bispecific antibody that neutralizes HIV-1 reduces the infectious titer of HIV-1. Broadly neutralizing bispecific antibodies to HIV-1 are distinct from other antibodies to HIV-1 in that they neutralize a high percentage of the many types of HIV-1 in circulation. In some implementations, broadly neutralizing antibodies to HIV-1 are distinct from other antibodies to HIV-1 in that they neutralize a high percentage (such as at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%) of the many types of HIV-1 in circulation. CD4: Cluster of differentiation factor 4 polypeptide; a T-cell surface protein that mediates interaction with the MHC class II molecule. CD4 also serves as the primary receptor site for HIV-1 on T-cells during HIV-1 infection. CD4 is known to bind to gp120 from HIV-1. The known sequence of the CD4 precursor has a hydrophobic signal peptide, an extracellular region of approximately 370 amino acids, a highly hydrophobic stretch with significant identity to the membrane-spanning domain of the class II MHC beta chain, and a highly charged intracellular sequence of 40 resides (Maddon, Cell 42:93, 1985). Conditions sufficient to form an immune complex: Conditions which allow an antibody to bind to its cognate epitope to a detectably greater degree than, and / or to the substantial exclusion of, binding to substantially all other epitopes. Conditions sufficient to form an immune complex are dependent upon the format of the binding reaction and typically are those utilized in immunoassay protocols or those conditions encountered in vivo. See Greenfield (Ed.), Antibodies: A Laboratory Manual, 2nded. New York: Cold Spring Harbor Laboratory Press, 2014, for a description of immunoassay formats and conditions. The conditions employed in the methods are “physiological conditions” which include reference to conditions (e.g., temperature, osmolarity, pH) that are typical inside a living mammal or a mammalian cell. While it is recognized that some organs are subject to extreme conditions, the intra-organismal and intracellular environment normally lies around pH 7 (e.g., from pH 6.0 to pH 8.0, more typically pH 6.5 to 7.5), contains water as the predominant solvent, and exists at a temperature above 0°C and below 50°C. Osmolarity is within the range that is supportive of cell viability and proliferation. The formation of an immune complex can be detected through conventional methods, for instance immunohistochemistry (IHC), immunoprecipitation (IP), flow cytometry, immunofluorescence microscopy, ELISA, immunoblotting (for example, Western blot),4239-111089-02magnetic resonance imaging (MRI), computed tomography (CT) scans, radiography, and affinity chromatography. Conjugate: A complex of two molecules linked together, for example, linked together by a covalent bond. In one implementation, an antibody is linked to an effector molecule; for example, an antibody that specifically binds to HIV-1 Env covalently linked to an effector molecule. The linkage can be by chemical or recombinant means. In one implementation, the linkage is chemical, wherein a reaction between the antibody moiety and the effector molecule has produced a covalent bond formed between the two molecules to form one molecule. A peptide linker (short peptide sequence) can optionally be included between the antibody and the effector molecule. Because conjugates can be prepared from two molecules with separate functionalities, such as an antibody and an effector molecule, they are also sometimes referred to as “chimeric molecules.” Conservative variants: “Conservative” amino acid substitutions are those substitutions that do not substantially affect or decrease a function of a protein, such as the ability of the protein to interact with a target protein. For example, a HIV-1 Env-specific antibody can include up to 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 conservative substitutions compared to a reference antibody sequence and retain specific binding activity for HIV-1 Env binding, and / or HIV-1 neutralization activity. The term conservative variation also includes the use of a substituted amino acid in place of an unsubstituted parent amino acid. Individual substitutions, deletions or additions which alter, add or delete a single amino acid or a small percentage of amino acids (for instance less than 5%, in some implementations less than 1%) in an encoded sequence are conservative variations where the alterations result in the substitution of an amino acid with a chemically similar amino acid. The following six groups are examples of amino acids that are considered to be conservative substitutions for one another: 1) Alanine (A), Serine (S), Threonine (T); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); and 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W). Contacting: Placement in direct physical association; includes both in solid and liquid form, which can take place either in vivo or in vitro. Contacting includes contact between one molecule and another molecule, for example the amino acid on the surface of4239-111089-02one polypeptide, such as an antigen, that contacts another polypeptide, such as an antibody. Contacting can also include contacting a cell for example by placing an antibody in direct physical association with a cell. Control: A reference standard. In some implementations, the control is a negative control, such as sample obtained from a healthy patient not infected with HIV-1. In other implementations, the control is a positive control, such as a tissue sample obtained from a patient diagnosed with HIV-1 infection. In still other implementations, the control is a historical control or standard reference value or range of values (such as a previously tested control sample, such as a group of HIV-1 patients with known prognosis or outcome, or group of samples that represent baseline or normal values). A difference between a test sample and a control can be an increase or conversely a decrease. The difference can be a qualitative difference or a quantitative difference, for example a statistically significant difference. In some examples, a difference is an increase or decrease, relative to a control, of at least about 5%, such as at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 100%, at least about 150%, at least about 200%, at least about 250%, at least about 300%, at least about 350%, at least about 400%, or at least about 500%. Degenerate variant: In the context of the present disclosure, a “degenerate variant” refers to a polynucleotide encoding a polypeptide (such as an antibody heavy or light chain) that includes a sequence that is degenerate as a result of the genetic code. There are 20 natural amino acids, most of which are specified by more than one codon. Therefore, all degenerate nucleotide sequences encoding a peptide are included as long as the amino acid sequence of the peptide encoded by the nucleotide sequence is unchanged. Detectable marker: A detectable molecule (also known as a label) that is conjugated directly or indirectly to a second molecule, such as an antibody, to facilitate detection of the second molecule. For example, the detectable marker can be capable of detection by ELISA, spectrophotometry, flow cytometry, microscopy or diagnostic imaging techniques (such as CT scans, MRIs, ultrasound, fiberoptic examination, and laparoscopic examination). Specific, non-limiting examples of detectable markers include fluorophores, chemiluminescent agents, enzymatic linkages, radioactive isotopes and heavy metals or compounds (for example super paramagnetic iron oxide nanocrystals for detection by MRI). Methods for using detectable markers and guidance in the choice of detectable markers appropriate for various purposes are discussed for example in Green and Sambrook4239-111089-02(Molecular Cloning: A Laboratory Manual, 4thed., New York: Cold Spring Harbor Laboratory Press, 2012) and Ausubel et al. (Eds.) (Current Protocols in Molecular Biology, New York: John Wiley and Sons, including supplements, 2017). Detecting: To identify the existence, presence, or fact of something. Effective amount: A quantity of a specific substance sufficient to achieve a desired effect in a subject to whom the substance is administered. For instance, this can be the amount necessary to prevent, treat (including prophylaxis), reduce and / or ameliorate the symptoms or underlying causes of a disorder or disease, such as HIV-1 infection. In some implementations, an effective amount of a disclosed bispecific or single- domain antibody is sufficient to reduce or eliminate a symptom of HIV-1 infection, such as AIDS. For instance, this can be the amount necessary to inhibit or prevent HIV-1 replication or to measurably alter outward symptoms of the HIV-1 infection. Ideally, the effective amount provides a therapeutic effect without causing a substantial cytotoxic effect in the subject. In some implementations, administration of an effective amount of a disclosed bispecific or single-domain antibody that binds to HIV-1 Env can reduce or inhibit an HIV-1 infection (for example, as measured by infection of cells, or by number or percentage of subjects infected by HIV-1, or by an increase in the survival time of infected subjects) by a desired amount, for example by at least 10%, at least 20%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or even at least 100% (elimination or prevention of detectable HIV-1 infection), as compared to a suitable control. An effective amount of a disclosed bispecific or single-domain antibody that specifically binds HIV-1 Env that is administered to a subject will vary depending upon a number of factors associated with that subject, for example the overall health and / or weight of the subject. An effective amount can be determined by varying the dosage and measuring the resulting therapeutic response, such as, for example, a reduction in viral titer. Therapeutically effective amounts also can be determined through various in vitro, in vivo or in situ immunoassays. An effective amount encompasses a fractional dose that contributes in combination with previous or subsequent administrations to attaining a therapeutic response. For example, an effective amount of an agent can be administered in a single dose, or in several doses, for example daily, during a course of treatment lasting several days or weeks. However, the effective amount can depend on the subject being treated, the severity and type of the condition being treated, and the manner of administration. A unit dosage form of the agent4239-111089-02can be packaged in a therapeutic amount, or in multiples of the therapeutic amount, for example, in a vial (e.g., with a pierceable lid) or syringe having sterile components. Effector molecule: A molecule intended to have or produce a desired effect; for example, a desired effect on a cell to which the effector molecule is targeted, or a detectable marker. Effector molecules can include, for example, polypeptides and small molecules. Some effector molecules may have or produce more than one desired effect. Epitope: An antigenic determinant. These are particular chemical groups or peptide sequences on a molecule that are antigenic, i.e. that elicit a specific immune response. An antibody specifically binds a particular antigenic epitope on a polypeptide. In some examples a disclosed bispecific antibody specifically binds to two different epitopes on HIV-1 Env. Expression: Transcription or translation of a nucleic acid sequence. For example, an encoding nucleic acid sequence (such as a gene) can be expressed when its DNA is transcribed into RNA or an RNA fragment, which in some examples is processed to become mRNA. An encoding nucleic acid sequence (such as a gene) may also be expressed when its mRNA is translated into an amino acid sequence, such as a protein or a protein fragment. In a particular example, a heterologous gene is expressed when it is transcribed into an RNA. In another example, a heterologous gene is expressed when its RNA is translated into an amino acid sequence. Regulation of expression can include controls on transcription, translation, RNA transport and processing, degradation of intermediary molecules such as mRNA, or through activation, inactivation, compartmentalization or degradation of specific protein molecules after they are produced. Expression Control Sequences: Nucleic acid sequences that regulate the expression of a heterologous nucleic acid sequence to which it is operatively linked. Expression control sequences are operatively linked to a nucleic acid sequence when the expression control sequences control and regulate the transcription and, as appropriate, translation of the nucleic acid sequence. Thus, expression control sequences can include appropriate promoters, enhancers, transcriptional terminators, a start codon (ATG) in front of a protein-encoding gene, splice signals for introns, maintenance of the correct reading frame of that gene to permit proper translation of mRNA, and stop codons. The term “control sequences” is intended to include, at a minimum, components whose presence can influence expression, and can also include additional components whose presence is advantageous, for example, leader sequences and fusion partner sequences. Expression control sequences can include a promoter.4239-111089-02Expression vector: A vector comprising a recombinant polynucleotide comprising expression control sequences operatively linked to a nucleotide sequence to be expressed. An expression vector comprises sufficient cis- acting elements for expression; other elements for expression can be supplied by the host cell or in an in vitro expression system. Non-limiting examples of expression vectors include cosmids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses) that incorporate the recombinant polynucleotide. A polynucleotide can be inserted into an expression vector that contains a promoter sequence which facilitates the efficient transcription of the inserted genetic sequence of the host. The expression vector typically contains an origin of replication, a promoter, as well as specific nucleic acid sequences that allow phenotypic selection of the transformed cells. Fc region: The constant region of an antibody excluding the first heavy chain constant domain. Fc region generally refers to the last two heavy chain constant domains of IgA, IgD, and IgG, and the last three heavy chain constant domains of IgE and IgM. An Fc region may also include part or all of the flexible hinge N-terminal to these domains. For IgA and IgM, an Fc region may or may not include the tailpiece, and may or may not be bound by the J chain. For IgG, the Fc region is typically understood to include immunoglobulin domains Cγ2 and Cγ3 and optionally the lower part of the hinge between Cγ1 and Cγ2. Although the boundaries of the Fc region may vary, the human IgG heavy chain Fc region is usually defined to include residues following C226 or P230 to the Fc carboxyl-terminus, wherein the numbering is according to EU numbering. For IgA, the Fc region includes immunoglobulin domains Cα2 and Cα3 and optionally the lower part of the hinge between Cα1 and Cα2. Heterologous: Originating from a different genetic source. A nucleic acid molecule that is heterologous to a cell originated from a genetic source other than the cell in which it is expressed. In one specific, non-limiting example, a heterologous nucleic acid molecule encoding a protein, such as an scFv, is expressed in a cell, such as a mammalian cell. Methods for introducing a heterologous nucleic acid molecule in a cell or organism are well known in the art, for example transformation with a nucleic acid, including electroporation, lipofection, particle gun acceleration, and homologous recombination. HIV-1 Envelope protein (Env): The HIV-1 envelope protein is initially synthesized as a precursor protein of 845-870 amino acids in size, designated gp160. Individual gp160 polypeptides form a homotrimer and undergo glycosylation within the Golgi apparatus as well as processing to remove the signal peptide, and cleavage by a cellular protease between4239-111089-02approximately positions 511 / 512 to generate separate gp120 and gp41 polypeptide chains, which remain associated as gp120 / gp41 protomers within the homotrimer. The ectodomain (that is, the extracellular portion) of the HIV-1 Env trimer undergoes several structural rearrangements from a prefusion mature (cleaved) closed conformation that evades antibody recognition, through intermediate conformations that bind to receptors CD4 and co-receptor (either CCR5 or CXCR4), to a postfusion conformation. HIV-1 gp120: A polypeptide that is part of the HIV-1 Env protein. Mature gp120 includes approximately HIV-1 Env residues 31-511, contains most of the external, surface- exposed, domains of the HIV-1 Env trimer, and it is gp120 which binds both to cellular CD4 receptors and to cellular chemokine receptors (such as CCR5). A mature gp120 polypeptide is an extracellular polypeptide that interacts with the gp41 ectodomain to form an HIV-1 Env protomer that trimerizes to form the HIV-1 Env trimer. HIV-1 gp41: A polypeptide that is part of the HIV-1 Env protein. Mature gp41 includes approximately HIV-1 Env residues 512-860, and includes cytosolic-, transmembrane-, and ecto-domains. The gp41 ectodomain (including approximately HIV-1 Env residues 512-644) can interact with gp120 to form an HIV-1 Env protomer that trimerizes to form the HIV-1 Env trimer. Human Immunodeficiency Virus type 1 (HIV-1): A retrovirus that causes immunosuppression in humans (HIV-1 disease), and leads to a disease complex known as the acquired immunodeficiency syndrome (AIDS). “HIV-1 disease” refers to a well-recognized constellation of signs and symptoms (including the development of opportunistic infections) in persons who are infected by an HIV-1 virus, as determined by antibody or western blot studies. Laboratory findings associated with this disease include a progressive decline in T cells. Related viruses that are used as animal models include simian immunodeficiency virus (SIV) and feline immunodeficiency virus (FIV). Treatment of HIV-1 with HAART has been effective in reducing the viral burden and ameliorating the effects of HIV-1 infection in infected individuals. Host cell: Cells in which a vector can be propagated and its nucleic acid expressed. The cell may be prokaryotic or eukaryotic. The term also includes any progeny of the subject host cell. It is understood that all progeny may not be identical to the parental cell since there may be mutations that occur during replication. However, such progeny are included when the term “host cell” is used. IgA: A polypeptide belonging to the class of antibodies that are substantially encoded by a recognized immunoglobulin alpha gene. In humans, this class or isotype comprises IgA14239-111089-02and IgA2. IgA antibodies can exist as monomers, polymers (referred to as pIgA) of predominantly dimeric form, and secretory IgA. The constant chain of wild-type IgA contains an 18-amino-acid extension at its C-terminus called the tail piece (tp). Polymeric IgA is secreted by plasma cells with a 15-kDa peptide called the J chain linking two monomers of IgA through the conserved cysteine residue in the tail piece. IgG: A polypeptide belonging to the class or isotype of antibodies that are substantially encoded by a recognized immunoglobulin gamma gene. In humans, this class comprises IgG1, IgG2, IgG3, and IgG4. Immune complex: The binding of antibody to a soluble antigen forms an immune complex. The formation of an immune complex can be detected through conventional methods, for instance immunohistochemistry, immunoprecipitation, flow cytometry, immunofluorescence microscopy, ELISA, immunoblotting (for example, Western blot), magnetic resonance imaging, CT scans, radiography, and affinity chromatography. Inhibiting a disease or condition: Reducing the full development of a disease or condition in a subject, for example, reducing the development of AIDS in a subject infected with HIV-1 or reducing symptoms associated with the HIV-1 infection. This includes neutralizing, antagonizing, prohibiting, preventing, restraining, slowing, disrupting, stopping, or reversing progression or severity of the disease or condition. Inhibiting a disease or condition includes a prophylactic intervention administered before the disease or condition has begun to develop (for example a treatment initiated in a subject at risk of an HIV-1 infection, but not infected by HIV-1) that reduces subsequent development of the disease or condition and also to amelioration of one or more signs or symptoms of the disease or condition following development. Additionally, inhibiting a disease or condition includes a therapeutic intervention administered after a disease or condition has begun to develop (for example, a treatment administered following diagnosis of a subject with HIV-1 infection) that ameliorates one or more signs or symptoms of the disease or condition in the subject. The term “ameliorating,” with reference to inhibiting a disease or condition refers to any observable beneficial effect of the intervention intended to inhibit the disease or condition. The beneficial effect can be evidenced, for example, by a delayed onset of clinical symptoms of the disease or condition in a susceptible subject, a reduction in severity of some or all clinical symptoms of the disease or condition, a slower progression of the disease or condition, an improvement in the overall health or well-being of the subject, a reduction in infection, or by other parameters that are specific to the particular disease or condition.4239-111089-02Isolated: A biological component (such as a nucleic acid, peptide, protein or protein complex, for example an antibody) that has been substantially separated, produced apart from, or purified away from other biological components in the cell of the organism in which the component naturally occurs, that is, other chromosomal and extra-chromosomal DNA and RNA, and proteins. Thus, isolated nucleic acids, peptides and proteins include nucleic acids and proteins purified by standard purification methods. The term also embraces nucleic acids, peptides and proteins prepared by recombinant expression in a host cell, as well as, chemically synthesized nucleic acids. An isolated nucleic acid, peptide or protein, for example an antibody, can be at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% pure. Kabat position: A position of a residue in an amino acid sequence that follows the numbering convention delineated by Kabat et al. (Sequences of Proteins of Immunological Interest, 5thEdition, Department of Health and Human Services, Public Health Service, National Institutes of Health, Bethesda, NIH Publication No.91-3242, 1991). Linker: A bi-functional molecule that can be used to link two molecules into one contiguous molecule, for example, to link a detectable marker to an antibody. Non-limiting examples of peptide linkers include glycine-serine linkers. The terms “conjugating,” “joining,” “bonding,” or “linking” can refer to making two molecules into one contiguous molecule; for example, linking two polypeptides into one contiguous polypeptide, or covalently attaching an effector molecule or detectable marker radionuclide or other molecule to a polypeptide, such as an scFv. The linkage can be either by chemical or recombinant means. “Chemical means” refers to a reaction between the antibody moiety and the effector molecule such that there is a covalent bond formed between the two molecules to form one molecule. Nucleic acid (molecule or sequence): A deoxyribonucleotide or ribonucleotide polymer or combination thereof including without limitation, cDNA, mRNA, genomic DNA, and synthetic (such as chemically synthesized) DNA or RNA. The nucleic acid can be double stranded (ds) or single stranded (ss). Where single stranded, the nucleic acid can be the sense strand or the antisense strand. Nucleic acids can include natural nucleotides (such as A, T / U, C, and G), and can include analogs of natural nucleotides, such as labeled nucleotides. “cDNA” refers to a DNA that is complementary or identical to an mRNA, in either single stranded or double stranded form. “Encoding” refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of4239-111089-02other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene encodes a protein if transcription and translation of mRNA produced by that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and non-coding strand, used as the template for transcription, of a gene or cDNA can be referred to as encoding the protein or other product of that gene or cDNA. Unless otherwise specified, a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. Nucleotide sequences that encode proteins and RNA may include introns. Operably linked: A first nucleic acid sequence is operably linked with a second nucleic acid sequence when the first nucleic acid sequence is placed in a functional relationship with the second nucleic acid sequence. For instance, a promoter, such as the CMV promoter, is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Generally, operably linked DNA sequences are contiguous and, where necessary to join two protein-coding regions, in the same reading frame. Pharmaceutically acceptable carriers: The pharmaceutically acceptable carriers of use are conventional. Remington: The Science and Practice of Pharmacy, 22nded., London, UK: Pharmaceutical Press, 2013, describes compositions and formulations suitable for pharmaceutical delivery of the disclosed agents. In general, the nature of the carrier will depend on the particular mode of administration being employed. For instance, parenteral formulations usually include injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle. For solid compositions (e.g., powder, pill, tablet, or capsule forms), conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate. In addition to biologically neutral carriers, pharmaceutical compositions to be administered can contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, added preservatives (such as non-natural preservatives), and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate. In particular examples, the pharmaceutically acceptable carrier is sterile and suitable for parenteral administration to a subject for example, by injection. In some4239-111089-02implementations, the active agent and pharmaceutically acceptable carrier are provided in a unit dosage form such as a pill or in a selected quantity in a vial. Unit dosage forms can include one dosage or multiple dosages (for example, in a vial from which metered dosages of the agents can selectively be dispensed). Polypeptide: A polymer in which the monomers are amino acid residues that are joined together through amide bonds. When the amino acids are alpha-amino acids, either the L-optical isomer or the D-optical isomer can be used, the L-isomers being preferred. The terms “polypeptide” or “protein” as used herein are intended to encompass any amino acid sequence and include modified sequences such as glycoproteins. A polypeptide includes both naturally occurring proteins, as well as those that are recombinantly or synthetically produced. A polypeptide has an amino terminal (N-terminal) end and a carboxy-terminal end. In some implementations, the polypeptide is a disclosed bispecific antibody. Purified: The term purified does not require absolute purity; rather, it is intended as a relative term. Thus, for example, a purified peptide preparation is one in which the peptide or protein (such as an antibody) is more enriched than the peptide or protein is in its natural environment within a cell. In one implementation, a preparation is purified such that the protein or peptide represents at least 50% of the total peptide or protein content of the preparation. Recombinant: A recombinant nucleic acid is one that has a sequence that is not naturally occurring or has a sequence that is made by an artificial combination of two otherwise separated segments of sequence. This artificial combination can be accomplished by chemical synthesis or, more commonly, by the artificial manipulation of isolated segments of nucleic acids, for example, by genetic engineering techniques. A recombinant protein is one that has a sequence that is not naturally occurring or has a sequence that is made by an artificial combination of two otherwise separated segments of sequence. In several implementations, a recombinant protein is encoded by a heterologous (for example, recombinant) nucleic acid that has been introduced into a host cell, such as a bacterial or eukaryotic cell. The nucleic acid can be introduced, for example, on an expression vector having signals capable of expressing the protein encoded by the introduced nucleic acid or the nucleic acid can be integrated into the host cell chromosome. Sequence identity: The identity between two or more nucleic acid sequences, or two or more amino acid sequences, is expressed in terms of the percentage identity between the sequences. Sequence identity can be measured in terms of percentage identity; the higher the percentage, the more identical the sequences. Homologs and variants of a VLor a VHof an4239-111089-02antibody that specifically binds a target antigen are typically characterized by possession of at least about 75% sequence identity, for example at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity counted over the full-length alignment with the amino acid sequence of interest. Any suitable method may be used to align sequences for comparison. Non-limiting examples of programs and alignment algorithms are described in: Smith and Waterman, Adv. Appl. Math.2(4):482-489, 1981; Needleman and Wunsch, J. Mol. Biol.48(3):443-453, 1970; Pearson and Lipman, Proc. Natl. Acad. Sci. U.S.A. 85(8):2444-2448, 1988; Higgins and Sharp, Gene, 73(1):237-244, 1988; Higgins and Sharp, Bioinformatics, 5(2):151-3, 1989; Corpet, Nucleic Acids Res.16(22):10881-10890, 1988; Huang et al. Bioinformatics, 8(2):155-165, 1992; and Pearson, Methods Mol. Biol.24:307-331, 1994., Altschul et al., J. Mol. Biol.215(3):403-410, 1990, presents a detailed consideration of sequence alignment methods and homology calculations. The NCBI Basic Local Alignment Search Tool (BLAST) (Altschul et al., J. Mol. Biol.215(3):403-410, 1990) is available from several sources, including the National Center for Biological Information and on the Internet, for use in connection with the sequence analysis programs blastp, blastn, blastx, tblastn, and tblastx. Blastn is used to compare nucleic acid sequences, while blastp is used to compare amino acid sequences. Additional information can be found at the NCBI web site. Generally, once two sequences are aligned, the number of matches is determined by counting the number of positions where an identical nucleotide or amino acid residue is present in both sequences. The percent sequence identity between the two sequences is determined by dividing the number of matches either by the length of the sequence set forth in the identified sequence, or by an articulated length (such as 100 consecutive nucleotides or amino acid residues from a sequence set forth in an identified sequence), followed by multiplying the resulting value by 100. Specifically bind: When referring to an antibody or antigen binding fragment, refers to a binding reaction which determines the presence of a target protein in the presence of a heterogeneous population of proteins and other biologics. Thus, under designated conditions, an antibody binds preferentially to a particular target protein, peptide or polysaccharide (such as an antigen present on the surface of a pathogen, for example HIV-1 Env and does not bind in a significant amount to other proteins present in the sample or subject. Specific binding can be determined by standard methods. See Harlow & Lane, Antibodies, A Laboratory Manual, 2nded., Cold Spring Harbor Publications, New York (2013), for a description of4239-111089-02immunoassay formats and conditions that can be used to determine specific immunoreactivity. With reference to an antibody-antigen complex, specific binding of the antigen and antibody has a KDof less than about 10-7Molar, such as less than about 10-8Molar, 10-9, or even less than about 10-10Molar. KD refers to the dissociation constant for a given interaction, such as a polypeptide ligand interaction or an antibody antigen interaction. For example, for the bimolecular interaction of an antibody or antigen binding fragment and an antigen it is the concentration of the individual components of the bimolecular interaction divided by the concentration of the complex. Subject: Living multicellular vertebrate organisms, a category that includes human and non-human mammals. In an example, a subject is a human. In a particular example, the subject is a newborn infant. In an additional example, a subject is selected that is in need of inhibiting an HIV-1 infection. For example, the subject is uninfected and at risk of HIV-1 infection. Transformed: A transformed cell is a cell into which a nucleic acid molecule has been introduced by molecular biology techniques. As used herein, the term transformed and the like (e.g., transformation, transfection, transduction, etc.) encompasses all techniques by which a nucleic acid molecule might be introduced into such a cell, including transduction with viral vectors, transformation with plasmid vectors, and introduction of DNA by electroporation, lipofection, and particle gun acceleration. Vector: An entity containing a nucleic acid molecule (such as a DNA molecule) bearing a promoter(s) that is operationally linked to the coding sequence of a protein of interest and can express the coding sequence. Non-limiting examples include a naked or packaged (lipid and / or protein) DNA, a subcomponent of a virus or bacterium or other microorganism that may be replication-incompetent, or a virus or bacterium or other microorganism that may be replication-competent. A vector is sometimes referred to as a construct. Recombinant DNA vectors are vectors having recombinant DNA. A vector can include nucleic acid sequences that permit it to replicate in a host cell, such as an origin of replication. A vector can also include one or more selectable marker genes and other genetic elements. Viral vectors are recombinant nucleic acid vectors having at least some nucleic acid sequences derived from one or more viruses. In some implementations, a viral vector comprises a nucleic acid molecule encoding a disclosed bispecific antibody that specifically binds to HIV-1 Env and neutralizes HIV. In some implementations, the viral vector can be an adeno-associated virus (AAV) vector.4239-111089-02Under conditions sufficient for: A phrase that is used to describe any environment that permits a desired activity. II. Description of Several Implementations Isolated bispecific antibodies that that specifically bind to the CD4 binding site and the V1-V2 region of HIV-1 Env trimer are provided. Also disclosed are single-domain antibodies that specifically bind human immunodeficiency virus 1 (HIV-1) Envelope (Env) protein. In some implementations, one or more of the single-domain antibodies are included in a disclosed bispecific antibody. The bispecific and single-domain antibodies neutralize HIV-1. Also disclosed herein are compositions including the bispecific and single-domain antibodies and a pharmaceutically acceptable carrier. Nucleic acids encoding the bispecific and single-domain antibodies and expression vectors (such as adeno-associated virus (AAV) viral vectors) including these nucleic acids are also provided. The bispecific and single-domain antibodies, nucleic acid molecules, and compositions can be used for research, diagnostic and therapeutic purposes. For example, the bispecific and single-domain antibodies can be used to diagnose or treat a subject with an HIV-1 infection, or can be administered prophylactically to prevent HIV-1 infection in a subject. A. Novel bispecific antibodies In some implementations, a bispecific antibody is provided, comprising a first binding domain and a second binding domain. The first binding domain comprises an antibody comprising a heavy chain variable region (VH) comprising a heavy chain variable region (VH) comprising a heavy chain complementarity determining region (HCDR)1, a HCDR2, and a HCDR3 of the VHsequence set forth as SEQ ID NO: 25 (CAP256V2LS), a light chain variable region (VL), and a constant domain, and specifically binds to the V1-V2 region of HIV-1 Env. The second binding domain comprises a single-domain antibody or multimer thereof of wherein the single-domain antibody comprises the complementarity determining region 1 (CDR1), CDR2 and CDR3 (e.g., as defined according to the Kabat or IMGT numbering system) of one of the single-domain antibody sequences set forth as (a) SEQ ID NO: 1 (G36), (b) SEQ ID NO: 5 (G36 K64E), (c) SEQ ID NO: 7 (R27), or (d) SEQ ID NO: 11 (R27 K64E), and specifically binds to a CD4 binding site of HIV-1 Env. The first and second binding domains can simultaneously bind to a single HIV-1 Env trimer. The C-4239-111089-02terminus of the single-domain antibody is fused to the N terminus of the VLby a peptide linker to form a single polypeptide chain. The bispecific antibody neutralizes HIV-1. In some implementations, the single-domain antibody of the second binding domain comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 2, 3, and 4, respectively. In some implementations, the single-domain antibody of the second binding domain comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 2, 6, and 4, respectively. In some implementations, the single-domain antibody of the second binding domain comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 8, 9, and 10, respectively. In some implementations, the single-domain antibody of the second binding domain comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 8, 12, and 10, respectively. In some implementations, the single-domain antibody of the second binding domain comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 2, 3, and 4, respectively, and the remainder of the single-domain antibody of the second binding domain is at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 1. In some implementations, the single-domain antibody of the second binding domain comprises an amino acid sequence set forth as SEQ ID NO: 1. In some implementations, the single-domain antibody of the second binding domain comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 2, 6, and 4, respectively, and the remainder of the single-domain antibody of the second binding domain is at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 5. In some implementations, the single-domain antibody of the second binding domain comprises an amino acid sequence set forth as SEQ ID NO: 5. In some implementations, the single-domain antibody of the second binding domain comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 8, 9, and 10, respectively, and the remainder of the single-domain antibody of the second binding domain is at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 7. In some implementations, the single-domain antibody of the second binding domain comprises an amino acid sequence set forth as SEQ ID NO: 7. In some implementations, the single-domain antibody of the second binding domain comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 8, 12, and 10, respectively, and the remainder of the single-domain antibody of the second binding domain is at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 11. In some4239-111089-02implementations, the single-domain antibody of the second binding domain comprises an amino acid sequence set forth as SEQ ID NO: 11. In some implementations, the single-domain antibody further comprises one or more amino acid substitutions in the framework regions to replace positively charged amino acids with neutral or negatively charged amino acids. For example, the single-domain antibody further comprises a R19E substitution in the framework region (FR) 1, or a K43E substitution in the FR2, or both the R19E and K43E substitutions (Kabat numbering). In some implementations, the single-domain antibody of the second binding domain comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 2, 3, and 4, respectively, and the remainder of the single-domain antibody is at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 1, and comprises one or more amino acid substitutions in the framework regions to replace positively charged amino acids with neutral or negatively charged amino acids. For example, the single-domain antibody further comprises a R19E substitution in the framework region (FR) 1, or a K43E substitution in the FR2, or both the R19E and K43E substitutions (Kabat numbering). In some implementations, the single-domain antibody of the second binding domain comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 2, 6, and 4, respectively, and the remainder of the single-domain antibody is at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 5 and comprises one or more amino acid substitutions in the framework regions to replace positively charged amino acids with neutral or negatively charged amino acids. For example, the single-domain antibody further comprises a R19E substitution in the framework region (FR) 1, or a K43E substitution in the FR2, or both the R19E and K43E substitutions (Kabat numbering). In some implementations, the single-domain antibody of the second binding domain comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 8, 9, and 10, respectively, and the remainder of the single-domain antibody is at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 7 and comprises one or more amino acid substitutions in the framework regions to replace positively charged amino acids with neutral or negatively charged amino acids. For example, the single-domain antibody further comprises a R19E substitution in the framework region (FR) 1, or a K43E substitution in the FR2, or both the R19E and K43E substitutions (Kabat numbering). In some implementations, the single-domain antibody of the second binding domain comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 8, 12, and 10, respectively, and the remainder of the single-domain antibody is at least 90% (such as at least4239-111089-0295% or at least 99%) identical to SEQ ID NO: 11 and comprises one or more amino acid substitutions in the framework regions to replace positively charged amino acids with neutral or negatively charged amino acids. For example, the single-domain antibody further comprises a R19E substitution in the framework region (FR) 1, or a K43E substitution in the FR2, or both the R19E and K43E substitutions (Kabat numbering). In some implementations, the single-domain antibody comprises or consists of the amino acid sequence set forth as any one of SEQ ID NO: 1 (G36), SEQ ID NO: 13 (G36 R19E), SEQ ID NO: 5 (G36 K64E), SEQ ID NO: 14 (G36 R19E, K43E, K64E), SEQ ID NO: 7 (R27), SEQ ID NO: 15 (R27 R19E), SEQ ID NO: 11 (R27 K64E), or SEQ ID NO: 16 (R27 R19E, K43E, K64E). In some implementations, the second binding domain comprises a multimer of the single-domain antibody, such as a dimer or a trimer of the single-domain antibody. In some implementations, the second binding domain comprises a trimer of the single-domain antibody comprising an amino acid sequence set forth as SEQ ID NO: 17 (G36x3), SEQ ID NO: 18 (G36x3 R19E), SEQ ID NO: 19 (G36x3 K64E), SEQ ID NO: 20 (G36x3 R19E, K43E, K64E), SEQ ID NO: 21 (R27x3), SEQ ID NO: 22 (R27x3 R19E), SEQ ID NO: 23 (R27x3 K64E), or SEQ ID NO: 24 (R27x3 R19E, K43E, K64E). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VHand a VLcomprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 1 (G36). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VHand a VLcomprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 13 (G36 R19E). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VHand a VLcomprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 5 (G36 K64E). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VHand a VLcomprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof4239-111089-02comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 14 (G36 R19E, K43E, K64E). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 7 (R27). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 15 (R27 R19E). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 11 (R27 K64E). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 16 (R27 R19E, K43E, K64E). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a multimer of a single-domain antibody comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 17 (G36x3). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a multimer of a single-domain antibody comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 18 (G36x3 R19E). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a multimer of a single-domain antibody comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 19 (G36x3 K64E). In some implementations of the bispecific antibody, the4239-111089-02antibody of the first binding domain comprises a VHand a VLcomprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a multimer of a single-domain antibody comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 20 (G36x3 R19E, K43E, K64E). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VHand a VLcomprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a multimer of a single-domain antibody comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 21 (R27x3). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VHand a VLcomprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a multimer of a single-domain antibody comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 22 (R27x3 R19E). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a multimer of a single-domain antibody comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 23 (R27x3 K64E). In some implementations of the bispecific antibody, the antibody of the first binding domain comprises a VHand a VLcomprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a multimer of a single-domain antibody comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 24 (R27x3 R19E, K43E, K64E). The peptide linker joining the single-domain antibody of the second binding domain to the light chain of the first binding domain can have any suitable length or composition of amino acids that allows for the bispecific antibody to simultaneously bind to the CD4 binding site (via the single-domain antibody of the second binding domain) and the V1-V2 region (via the antibody of the first binding domain) of HIV-1 Env trimer. In some implementations, the peptide linker is from 5-30 amino acids in length, such as from 10-30, from 15-30, from 10-20, from 20-30, from 12-17, or from 14-16 amino acids in length. In some implementations, the peptide linker is 5, 10, 15, 20, 25, or 30 amino acids in length. In some implementations, the peptide linker is a glycine-serine linker. In some implementations, the peptide linker comprises a human IgG1 hinge sequence or a multiple thereof, such as from 1-3 repeats of the hinge sequence. In some implementations, the peptide linker comprises or consists of an amino acid sequence set forth as any one of the4239-111089-02following: GGSGG (SEQ ID NO: 44), GGSGGGGSGG (SEQ ID NO: 45), GGSGGGGSGGGGSGG (SEQ ID NO: 43), DKTHT (SEQ ID NO: 46), DKTHTGDKTHT (SEQ ID NO: 47), or DKTHTGDKTHTGDKTHT (SEQ ID NO: 48). In several implementations, the peptide liner comprises or consists of the amino acid sequence set forth as SEQ ID NO: 43 (GGSGGGGSGGGGSGG). In some implementations, the HCDR1, HCDR2, and HCDR3 of the VHof the antibody of the first binding domain comprise amino acid sequences set forth as SEQ ID NOs: 26, 27, and 28, respectively. In some implementations, the VHof the antibody of the first binding domain comprises the HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 26, 27, and 28, respectively, and the remainder of the VHis at least 90% identical to SEQ ID NO: 25. In some implementations, the VH of the antibody of the first binding domain comprises an amino acid sequence set forth as SEQ ID NO: 25. In some implementations, the VL of the antibody of the first binding domain comprises a light chain complementarity determining region (LCDR)1, a LCDR2, and a LCDR3 comprising amino acid sequences set forth as SEQ ID NOs: 30, 31, and 32, respectively. In some implementations, the VL of the antibody of the first binding domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 29. In some implementations, the VL of the antibody of the first binding domain comprises a LCDR1, a LCDR2, and a LCDR3 comprising amino acid sequences set forth as SEQ ID NOs: 30, 31, and 32, respectively, and the remaining amino acid sequence of the VL is at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 29. In some implementations, the VL of the antibody of the first binding domain comprises an amino acid sequence set forth as SEQ ID NO: 29. In some implementations, the fusion protein including the single-domain antibody of the second binding domain fused to the VLof the light chain of the antibody of the first binding domain by the peptide linker comprises the amino acid sequence set forth as any one of amino acids 1-251 of SEQ ID NO: 33 or 34, amino acids 1-531 of SEQ ID NO: 35, 36, or 37, amino acids 1-247 of SEQ ID NO: 38 or 39, or amino acids 1-519 of SEQ ID NO: 40, 41, or 42. In some implementations, the fusion protein including the single-domain antibody of the second binding domain fused to the light chain of the antibody of the first binding domain by the peptide linker comprises the amino acid sequence set forth as any one of SEQ ID NOs: 33-42. The antibody of the first binding domain can be in any suitable format that allows for fusion of the single-domain antibody to the N-terminus of the light chain of the antibody and4239-111089-02for simultaneous binding of the single-domain antibody to the CD4 binding site of HIV-1 Env and the antibody of the first binding domain to the V1-V2 region of HIV-1 Env. In some implementations, the antibody has an IgG, IgM or IgA format. In several implementations, the antibody of the first binding domain comprises a constant domain comprising a modification that increases binding to the neonatal Fc receptor. In some implementations, the constant domain comprises M428L and N434S mutations (“LS” mutation) according to EU numbering. In some implementations, the heavy chain of the antibody of the first binding domain comprises the amino acid sequence set forth as SEQ ID NO: 30 and the single-domain antibody fused to the light chain of the antibody comprises the amino acid sequence set forth as any one of SEQ ID NOs: 33-42. In some implementations, the heavy chain of the antibody of the first binding domain comprises the amino acid sequence set forth as SEQ ID NO: 30 and the single-domain antibody fused to the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO: 33. In some implementations, the heavy chain of the antibody of the first binding domain comprises the amino acid sequence set forth as SEQ ID NO: 30 and the single-domain antibody fused to the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO: 34. In some implementations, the heavy chain of the antibody of the first binding domain comprises the amino acid sequence set forth as SEQ ID NO: 30 and the single-domain antibody fused to the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO: 35. In some implementations, the heavy chain of the antibody of the first binding domain comprises the amino acid sequence set forth as SEQ ID NO: 30 and the single-domain antibody fused to the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO: 36. In some implementations, the heavy chain of the antibody of the first binding domain comprises the amino acid sequence set forth as SEQ ID NO: 30 and the single-domain antibody fused to the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO: 37. In some implementations, the heavy chain of the antibody of the first binding domain comprises the amino acid sequence set forth as SEQ ID NO: 30 and the single-domain antibody fused to the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO: 38. In some implementations, the heavy chain of the antibody of the first binding domain comprises the amino acid sequence set forth as SEQ ID NO: 30 and the single-domain antibody fused to the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO: 39. In some implementations, the heavy chain of the antibody of the first binding domain comprises the amino acid sequence set forth as4239-111089-02SEQ ID NO: 30 and the single-domain antibody fused to the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO: 40. In some implementations, the heavy chain of the antibody of the first binding domain comprises the amino acid sequence set forth as SEQ ID NO: 30 and the single-domain antibody fused to the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO: 41. In some implementations, the heavy chain of the antibody of the first binding domain comprises the amino acid sequence set forth as SEQ ID NO: 30 and the single-domain antibody fused to the light chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO: 42. The single-domain antibody of the second binding domain and the VL and VH of the first binding domain can include any suitable framework region, such as (but not limited to) a human framework region. The antibody of the first binding domain can be of any isotype. The antibody can be, for example, an IgM or an IgG antibody, such as IgG1, IgG2, IgG3, or IgG4. The class of an antibody that specifically binds HIV-1 Env can be switched with another. In one aspect, a nucleic acid molecule encoding VL or VH is isolated using methods well-known in the art, such that it does not include any nucleic acid sequences encoding the constant region of the light or heavy chain, respectively. A nucleic acid molecule encoding VLor VHis then operatively linked to a nucleic acid sequence encoding a CL or CH from a different class of immunoglobulin molecule. This can be achieved using a vector or nucleic acid molecule that comprises a CL or CH chain, as known in the art. For example, an antibody that specifically binds HIV-1 Env, that was originally IgG may be class switched to an IgM. Class switching can be used to convert one IgG subclass to another, such as from IgG1 to IgG2, IgG3, or IgG4. B. Novel single-domain antibodies In some implementations, a single-domain antibody or multimer thereof is provided that specifically binds human immunodeficiency virus 1 (HIV-1) Envelope (Env) protein. The single-domain antibody or multimer thereof neutralizes HIV-1. The single-domain antibody comprises the complementarity determining region 1 (CDR1), CDR2 and CDR3 sequences of SEQ ID NO: 1 (G36), SEQ ID NO: 5 (G36 K64E), SEQ ID NO: 7 (R27) or SEQ ID NO: 11 (R27 K64E). In some implementations, the CDR sequences are defined according to the Kabat or IMGT convention. In some implementations, the single-domain antibody comprises CDR1, CDR2, and CDR3 sequences set forth as SEQ ID NOs: 2, 3, and 4, respectively. In some implementations, the single-domain antibody comprises CDR1, CDR2, and CDR3 sequences4239-111089-02set forth as SEQ ID NOs: 2, 3, and 4, respectively, and the remaining portion of the single- domain antibody comprises an amino acid sequence at least 90% identical to SEQ ID NO: 1. In some implementations, the single-domain antibody comprises CDR1, CDR2, and CDR3 sequences set forth as SEQ ID NOs: 2, 3, and 4, respectively. In some implementations, the single-domain antibody comprises CDR1, CDR2, and CDR3 sequences set forth as SEQ ID NOs: 2, 6, and 4, respectively, and the remaining portion of the single- domain antibody comprises an amino acid sequence at least 90% identical to SEQ ID NO: 5. In some implementations, the single-domain antibody comprises CDR1, CDR2, and CDR3 sequences set forth as SEQ ID NOs: 8, 9, and 10, respectively. In some implementations, the single-domain antibody comprises CDR1, CDR2, and CDR3 sequences set forth as SEQ ID NOs: 8, 9, and 10, respectively, and the remaining portion of the single- domain antibody comprises an amino acid sequence at least 90% identical to SEQ ID NO: 7. In some implementations, the single-domain antibody comprises CDR1, CDR2, and CDR3 sequences set forth as SEQ ID NOs: 8, 12, and 10, respectively. In some implementations, the single-domain antibody comprises CDR1, CDR2, and CDR3 sequences set forth as SEQ ID NOs: 8, 12, and 10, respectively, and the remaining portion of the single- domain antibody comprises an amino acid sequence at least 90% identical to SEQ ID NO: 11. In some implementations, the single-domain antibody further comprises one or more amino acid substitutions in the framework regions to replace positively charged amino acids with neutral or negatively charged amino acids. For example, the single-domain antibody further comprises a R19E substitution in the framework region (FR) 1, or a K43E substitution in the FR2, or both the R19E and K43E substitutions (Kabat numbering). In some implementations, the single-domain antibody comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 2, 3, and 4, respectively, and the remainder of the single-domain antibody is at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 1, and comprises one or more amino acid substitutions in the framework regions to replace positively charged amino acids with neutral or negatively charged amino acids. For example, the single-domain antibody further comprises a R19E substitution in the framework region (FR) 1, or a K43E substitution in the FR2, or both the R19E and K43E substitutions (Kabat numbering). In some implementations, the single-domain antibody comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 2, 6, and 4, respectively, and the remainder of the single-domain antibody is at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 5 and comprises one or more amino acid substitutions in the framework regions4239-111089-02to replace positively charged amino acids with neutral or negatively charged amino acids. For example, the single-domain antibody further comprises a R19E substitution in the framework region (FR) 1, or a K43E substitution in the FR2, or both the R19E and K43E substitutions (Kabat numbering). In some implementations, the single-domain antibody comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 8, 9, and 10, respectively, and the remainder of the single-domain antibody is at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 7 and comprises one or more amino acid substitutions in the framework regions to replace positively charged amino acids with neutral or negatively charged amino acids. For example, the single-domain antibody further comprises a R19E substitution in the framework region (FR) 1, or a K43E substitution in the FR2, or both the R19E and K43E substitutions (Kabat numbering). In some implementations, the single-domain antibody comprises the CDR1, CDR2, and CDR3 set forth as SEQ ID NOs: 8, 12, and 10, respectively, and the remainder of the single-domain antibody is at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 11 and comprises one or more amino acid substitutions in the framework regions to replace positively charged amino acids with neutral or negatively charged amino acids. For example, the single-domain antibody further comprises a R19E substitution in the framework region (FR) 1, or a K43E substitution in the FR2, or both the R19E and K43E substitutions (Kabat numbering). In some implementations, the single-domain antibody comprises or consists of the amino acid sequence set forth as any one of SEQ ID NO: 1 (G36), SEQ ID NO: 13 (G36 R19E), SEQ ID NO: 5 (G36 K64E), SEQ ID NO: 14 (G36 R19E, K43E, K64E), SEQ ID NO: 7 (R27), SEQ ID NO: 15 (R27 R19E), SEQ ID NO: 11 (R27 K64E), or SEQ ID NO: 16 (R27 R19E, K43E, K64E). In some implementations, a multimer of the single-domain antibody is provided, such as a dimer or a trimer of the single-domain antibody. In some implementations, a trimer of the single-domain antibody is provided, comprising an amino acid sequence set forth as SEQ ID NO: 17 (G36x3), SEQ ID NO: 18 (G36x3 R19E), SEQ ID NO: 19 (G36x3 K64E), SEQ ID NO: 20 (G36x3 R19E, K43E, K64E), SEQ ID NO: 21 (R27x3), SEQ ID NO: 22 (R27x3 R19E), SEQ ID NO: 23 (R27x3 K64E), or SEQ ID NO: 24 (R27x3 R19E, K43E, K64E). Also provided is a fusion protein comprising the single-domain antibody or multimer thereof as provided herein fused to a heterologous protein. In some implementations, the heterologous protein comprises a human Fc protein. In some implementations, the human Fc4239-111089-02protein comprises a modification that increases half-life of the fusion protein, such as a modification that increases binding to the neonatal Fc receptor. In some implementations, any one of the single-domain antibodies or multimers thereof as provided herein is fused to an IgG2a Fc region, such as the IgG2a Fc region set forth as SEQ ID NO: 51. In some implementations, the single-domain antibody or multimer thereof fused to the IgG2a Fc region comprises an amino acid sequence set forth as SEQ ID NO: 52 (G36x3-IgG2a) or SEQ ID NO: 53 (R27x3-IgG2a). Also provided is a multispecific antibody comprising the single-domain antibody or multimer thereof as provided herein, such as a bispecific antibody or a trispecific antibody. Any suitable multispecific antibody format can be used to incorporate the single-domain antibody or multimer thereof as provided herein. C. Additional Description of the bispecific and single-domain antibodies The bispecific and / or single-domain antibody or multimer thereof can be derivatized or linked to another molecule (such as another peptide or protein). In general, the bispecific and / or single-domain antibody or multimer thereof is derivatized such that the binding to HIV-1 Env is not affected adversely by the derivatization or labeling. For example, the bispecific and / or single-domain antibody or multimer thereof can be functionally linked (by chemical coupling, genetic fusion, noncovalent association or otherwise) to one or more other molecular entities, such as another antibody, a detectable marker, an effector molecule, or a protein or peptide that can mediate association of the bispecific antibody with another molecule (such as a streptavidin core region or a polyhistidine tag). In several implementations, the bispecific and / or single-domain antibody or multimer thereof specifically binds HIV-1 Env with an affinity (e.g., measured by KD) of no more than 25 nM, such as no more than 20 nM, no mor than 15nM, or no more than 10 nM. KDcan be measured, for example, by a radiolabeled antigen binding assay (RIA) performed with the Fab version of an antibody of interest and its antigen, or isothermal calorimetry (ITC) using known methods. In some implementations, the bispecific and / or single-domain antibody or multimer thereof can be distinguished by neutralization breadth. In some implementations, the bispecific antibody neutralizes at least 95% (such as at least 96%, at least 97%, at least 98% or at least 99%) of the HIV-1 isolates included in a standardized panel of HIV-1 pseudoviruses (such as the panel of 208 diverse HIV-1 pseudoviruses described in Kwon et al., Cell Reports, 22, 1798-1809, 2018) with an IC50of less than 50 µg / ml. The person of4239-111089-02ordinary skill in the art is familiar with methods of measuring neutralization breadth and potency, for example such methods include the single-round HIV-1 Env-pseudoviruses infection of TZM-bl cells (see, e.g., Li et al., J Virol 79, 10108-10125, 2005; see also, PCT Pub. No. WO2011 / 038290). In some implementations, amino acid sequence variants of the bispecific and / or single-domain antibody or multimer thereof provided herein are provided. For example, it may be desirable to improve the binding affinity and / or other biological properties of the bispecific and / or single-domain antibody or multimer thereof. Amino acid sequence variants of the bispecific and / or single-domain antibody or multimer thereof may be prepared, for example, by introducing appropriate modifications into the nucleotide sequence encoding the antibody VH domain and / or VL domain, or the single-domain antibody. Such modifications include, for example, deletions from, and / or insertions into and / or substitutions of residues within the amino acid sequences of the antibody. Any combination of deletion, insertion, and substitution can be made to arrive at the final construct, provided that the final construct possesses the desired characteristics, e.g., antigen-binding. In some implementations, variants having one or more amino acid substitutions are provided. Sites of interest for substitutional mutagenesis include the CDRs and the framework regions. Amino acid substitutions may be introduced into an antibody of interest and the products screened for a desired activity, e.g., retained / improved antigen binding, decreased immunogenicity, or improved ADCC or CDC. The variants typically retain amino acid residues necessary for correct folding and stabilizing between the VH and the VL regions, and will retain the charge characteristics of the residues in order to preserve the low pI and low toxicity of the molecules. Amino acid substitutions can be made in the VH and the VL regions, the constant region, or the single- domain antibody, for example, to increase yield. In some implementations, substitutions, insertions, or deletions may occur within one or more CDRs so long as such alterations do not substantially reduce the ability of the antibody to bind antigen. For example, conservative alterations (e.g., conservative substitutions as provided herein) that do not substantially reduce binding affinity may be made in CDRs. In some implementations of the variant bispecific or single-domain antibody, or VH, and VL sequences provided above, each CDR either is unaltered, or contains no more than one, two or three amino acid substitutions. In some implementations of the variant VHand VL sequences provided above, only the framework residues are modified so the CDRs are unchanged.4239-111089-02To increase binding affinity of the bispecific and / or single-domain antibody or multimer thereof, the VLand VHsegments can be randomly mutated in a process analogous to the in vivo somatic mutation process responsible for affinity maturation of antibodies during a natural immune response. Thus in vitro affinity maturation can be accomplished by amplifying VH and VL regions using PCR primers complementary to selected regions, such as the HCDR3. In this process, the primers have been “spiked” with a random mixture of the four nucleotide bases at certain positions such that the resultant PCR products encode VH and VLsegments into which random mutations have been introduced into the CDR3 regions. These randomly mutated VH and VL segments can be tested to determine the binding affinity for HIV-1 Env. In some implementations, a bispecific and / or single-domain antibody or multimer thereof disclosed herein is altered to increase or decrease the extent to which the antibody is glycosylated. Addition or deletion of glycosylation sites may be conveniently accomplished by altering the amino acid sequence such that one or more glycosylation sites is created or removed. Where the bispecific and / or single-domain antibody or multimer thereof comprises or is fused to an Fc region, the carbohydrate attached thereto may be altered. Native antibodies produced by mammalian cells typically comprise a branched, biantennary oligosaccharide that is generally attached by an N-linkage to Asn297 of the CH2domain of the Fc region. See, e.g., Wright et al. Trends Biotechnol.15(1):26-32, 1997. The oligosaccharide may include various carbohydrates, e.g., mannose, N-acetyl glucosamine (GlcNAc), galactose, and sialic acid, as well as a fucose attached to a GlcNAc in the “stem” of the biantennary oligosaccharide structure. In some implementations, modifications of the oligosaccharide in an antibody may be made in order to create antibody variants with certain improved properties. In one implementation, variants are provided having a carbohydrate structure that lacks fucose attached (directly or indirectly) to an Fc region. For example, the amount of fucose in such antibody may be from 1% to 80%, from 1% to 65%, from 5% to 65% or from 20% to 40%. The amount of fucose is determined by calculating the average amount of fucose within the sugar chain at Asn297, relative to the sum of all glycostructures attached to Asn 297 (e.g. complex, hybrid and high mannose structures) as measured by MALDI-TOF mass spectrometry, as described in WO 2008 / 077546, for example. Asn297 refers to the asparagine residue located at about position 297 in the Fc region; however, Asn297 may also be located about ±3 amino acids upstream or downstream of position 297, i.e., between4239-111089-02positions 294 and 300, due to minor sequence variations in antibodies. Such fucosylation variants may have improved ADCC function. See, e.g., US Patent Publication Nos. US 2003 / 0157108 (Presta, L.); US 2004 / 0093621 (Kyowa Hakko Kogyo Co., Ltd). Examples of publications related to “defucosylated” or “fucose-deficient” antibody variants include: US 2003 / 0157108; WO 2000 / 61739; WO 2001 / 29246; US 2003 / 0115614; US 2002 / 0164328; US 2004 / 0093621; US 2004 / 0132140; US 2004 / 0110704; US 2004 / 0110282; US 2004 / 0109865; WO 2003 / 085119; WO 2003 / 084570; WO 2005 / 035586; WO 2005 / 035778; WO2005 / 053742; WO 2002 / 031140; Okazaki et al., J. Mol. Biol., 336(5):1239-1249, 2004; Yamane-Ohnuki et al., Biotechnol. Bioeng.87(5):614-622, 2004. Examples of cell lines capable of producing defucosylated antibodies include Lec 13 CHO cells deficient in protein fucosylation (Ripka et al., Arch. Biochem. Biophys.249(2):533-545, 1986; US Pat. Appl. No. US 2003 / 0157108 and WO 2004 / 056312, especially at Example 11), and knockout cell lines, such as alpha-1,6-fucosyltransferase gene, FUT8, knockout CHO cells (see, e.g., Yamane- Ohnuki et al., Biotechnol. Bioeng., 87(5): 614-622, 2004; Kanda et al., Biotechnol. Bioeng., 94(4):680-688, 2006; and WO2003 / 085107). Antibody variants are further provided with bisected oligosaccharides, e.g., in which a biantennary oligosaccharide attached to the Fc region of the antibody is bisected by GlcNAc. Such antibody variants may have reduced fucosylation and / or improved ADCC function. Examples of such antibody variants are described, e.g., in WO 2003 / 011878 (Jean-Mairet et al.); U.S. Pat. No.6,602,684 (Umana et al.); and US 2005 / 0123546 (Umana et al.). Antibody variants with at least one galactose residue in the oligosaccharide attached to the Fc region are also provided. Such antibody variants may have improved CDC function. Such antibody variants are described, e.g., in WO 1997 / 30087; WO 1998 / 58964; and WO 1999 / 22764. In several implementations, the constant region of the antibody comprises one or more amino acid substitutions to optimize in vivo half-life of the antibody. The serum half- life of IgG Abs is regulated by the neonatal Fc receptor (FcRn). Thus, in several implementations, the antibody comprises an amino acid substitution that increases binding to the FcRn. Non-limiting examples of such substitutions include substitutions at IgG constant regions T250Q and M428L (see, e.g., Hinton et al., J Immunol., 176(1):346-356, 2006); M428L and N434S (numbering according to EU system) called the “LS” mutation, see, e.g., Zalevsky, et al., Nature Biotechnol., 28(2):157-159, 2010); N434A (see, e.g., Petkova et al., Int. Immunol., 18(12):1759-1769, 2006); T307A, E380A, and N434A (see, e.g., Petkova et al., Int. Immunol., 18(12):1759-1769, 2006); and M252Y, S254T, and T256E (see, e.g., Dall’Acqua et al., J. Biol. Chem., 281(33):23514-23524, 2006). The disclosed antibodies can4239-111089-02be linked to or comprise an Fc polypeptide including any of the substitutions listed above, for example, the Fc polypeptide can include the M428L and N434S substitutions. In some implementations, a bispecific and / or single-domain antibody or multimer thereof provided herein may be further modified to contain additional nonproteinaceous moieties. The moieties suitable for derivatization of the antibody include but are not limited to water soluble polymers. Non-limiting examples of water soluble polymers include, but are not limited to, polyethylene glycol (PEG), copolymers of ethylene glycol / propylene glycol, carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone, poly-1,3- dioxolane, poly-1,3,6-trioxane, ethylene / maleic anhydride copolymer, polyaminoacids (either homopolymers or random copolymers), and dextran or poly(n-vinyl pyrrolidone)polyethylene glycol, propropylene glycol homopolymers, prolypropylene oxide / ethylene oxide co- polymers, polyoxyethylated polyols (e.g., glycerol), polyvinyl alcohol, and mixtures thereof. Polyethylene glycol propionaldehyde may have advantages in manufacturing due to its stability in water. The polymer may be of any molecular weight, and may be branched or unbranched. The number of polymers attached to the antibody may vary, and if more than one polymer are attached, they can be the same or different molecules. In general, the number and / or type of polymers used for derivatization can be determined based on considerations including, but not limited to, the particular properties or functions of the antibody to be improved, whether the antibody derivative will be used in an application under defined conditions, etc. D. Polynucleotides and Expression Nucleic acid molecules (for example, cDNA or RNA molecules) encoding the amino acid sequences of the disclosed bispecific and / or single-domain antibody or multimer thereof are provided. Nucleic acids encoding these molecules can readily be produced using the amino acid sequences provided herein (such as the CDR sequences and VH, VL, and single- domain antibody sequences), sequences available in the art (such as framework or constant region sequences), and the genetic code. In several implementations, nucleic acid molecules can encode the VH, the single-domain antibody fused to the VL, or both the VH and the single- domain antibody fused to the VL(for example in a bicistronic expression vector) of a disclosed bispecific antibody. In several implementations, the nucleic acid molecules can be expressed in a host cell (such as a mammalian cell) to produce a disclosed antibody. The genetic code can be used to construct a variety of functionally equivalent nucleic acid sequences, such as nucleic acids which differ in sequence but which encode the same4239-111089-02antibody sequence or a conjugate or fusion protein including the single-domain antibody fused to the VLand / or VHof the bispecific antibody. In a non-limiting example, an isolated nucleic acid molecule encodes the VH of a disclosed bispecific antibody. In another non-limiting example, the nucleic acid molecule encodes the single-domain antibody fused to the VL of a disclosed bispecific antibody. In another non-limiting example, the nucleic acid molecule encodes a single-domain antibody or multimer thereof as disclosed herein. Nucleic acid molecules encoding the bispecific antibodies and conjugates that specifically bind HIV-1 Env can be prepared by any suitable method including, for example, cloning of appropriate sequences or by direct chemical synthesis by standard methods. Chemical synthesis produces a single stranded oligonucleotide. This can be converted into double stranded DNA by hybridization with a complementary sequence or by polymerization with a DNA polymerase using the single strand as a template. Exemplary nucleic acids can be prepared by cloning techniques. Examples of appropriate cloning and sequencing techniques can be found, for example, in Green and Sambrook (Molecular Cloning: A Laboratory Manual, 4thed., New York: Cold Spring Harbor Laboratory Press, 2012) and Ausubel et al. (Eds.) (Current Protocols in Molecular Biology, New York: John Wiley and Sons, including supplements, 2017). Nucleic acids can also be prepared by amplification methods. Amplification methods include the polymerase chain reaction (PCR), the ligase chain reaction (LCR), the transcription-based amplification system (TAS), and the self-sustained sequence replication system (3SR). The nucleic acid molecules can be expressed in a recombinantly engineered cell such as bacteria, plant, yeast, insect and mammalian cells. The bispecific antibodies can be expressed as individual proteins including the VHand / or the single-domain antibody fused to the VL (linked to an effector molecule or detectable marker as needed), or can be expressed as a fusion protein. Any suitable method of expressing and purifying antibodies may be used; non-limiting examples are provided in Al-Rubeai (Ed.), Antibody Expression and Production, Dordrecht; New York: Springer, 2011). An immunoadhesin can also be expressed. Thus, in some examples, nucleic acids encoding a VHand the single-domain antibody fused to the VL, and immunoadhesin are provided. The nucleic acid sequences can optionally encode a leader sequence. One or more DNA sequences encoding the antibodies or conjugates can be expressed in vitro by DNA transfer into a suitable host cell. The cell may be prokaryotic or eukaryotic.4239-111089-02Numerous expression systems available for expression of proteins including E. coli, other bacterial hosts, yeast, and various higher eukaryotic cells such as the COS, CHO, HeLa and myeloma cell lines, can be used to express the disclosed bispecific antibodies. Methods of stable transfer, meaning that the foreign DNA is continuously maintained in the host, are known in the art. Hybridomas expressing the antibodies of interest are also encompassed by this disclosure. The expression of nucleic acids encoding the bispecific and single-domain antibodies described herein can be achieved by operably linking the DNA or cDNA to a promoter (which is either constitutive or inducible), followed by incorporation into an expression cassette. The promoter can be any promoter of interest, including a cytomegalovirus promoter. Optionally, an enhancer, such as a cytomegalovirus enhancer, is included in the construct. The cassettes can be suitable for replication and integration in either prokaryotes or eukaryotes. Typical expression cassettes contain specific sequences useful for regulation of the expression of the DNA encoding the protein. For example, the expression cassettes can include appropriate promoters, enhancers, transcription and translation terminators, initiation sequences, a start codon (i.e., ATG) in front of a protein-encoding gene, splicing signals for introns, sequences for the maintenance of the correct reading frame of that gene to permit proper translation of mRNA, and stop codons. The vector can encode a selectable marker, such as a marker encoding drug resistance (for example, ampicillin or tetracycline resistance). To obtain high level expression of a cloned gene, it is desirable to construct expression cassettes which contain, for example, a strong promoter to direct transcription, a ribosome binding site for translational initiation (e.g., internal ribosomal binding sequences), and a transcription / translation terminator. For E. coli, this can include a promoter such as the T7, trp, lac, or lamda promoters, a ribosome binding site, and preferably a transcription termination signal. For eukaryotic cells, the control sequences can include a promoter and / or an enhancer derived from, for example, an immunoglobulin gene, HTLV, SV40 or cytomegalovirus, and a polyadenylation sequence, and can further include splice donor and / or acceptor sequences (for example, CMV and / or HTLV splice acceptor and donor sequences). The cassettes can be transferred into the chosen host cell by any suitable method such as transformation or electroporation for E. coli and calcium phosphate treatment, electroporation or lipofection for mammalian cells. Cells transformed by the cassettes can be selected by resistance to antibiotics conferred by genes contained in the cassettes, such as the amp, gpt, neo and hyg genes.4239-111089-02Modifications can be made to a nucleic acid encoding a polypeptide described herein without diminishing its biological activity. Some modifications can be made to facilitate the cloning, expression, or incorporation of the targeting molecule into a fusion protein. Such modifications include, for example, termination codons, sequences to create conveniently located restriction sites, and sequences to add a methionine at the amino terminus to provide an initiation site, or additional amino acids (such as poly His) to aid in purification steps. Once expressed, the bispecific and single-domain antibodies can be purified according to standard procedures in the art, including ammonium sulfate precipitation, affinity columns, column chromatography, and the like (see, generally, Simpson et al. (Eds.), Basic methods in Protein Purification and Analysis: A Laboratory Manual, New York: Cold Spring Harbor Laboratory Press, 2009). The bispecific antibodies and conjugates need not be 100% pure. Once purified, partially or to homogeneity as desired, if to be used prophylatically, the polypeptides should be substantially free of endotoxin. Methods for expression of antibodies and / or refolding to an appropriate active form, from mammalian cells, and bacteria such as E. coli have been described and are applicable to the antibodies disclosed herein. See, e.g., Greenfield (Ed.), Antibodies: A Laboratory Manual, 2nded. New York: Cold Spring Harbor Laboratory Press, 2014, Simpson et al. (Eds.), Basic methods in Protein Purification and Analysis: A Laboratory Manual, New York: Cold Spring Harbor Laboratory Press, 2009, and Ward et al., Nature 341(6242):544- 546, 1989. E. Methods and Compositions 1. Therapeutic Methods Methods are disclosed herein for the inhibition of an HIV-1 infection in a subject. The methods include administering to a subject an effective amount (that is, an amount effective to inhibit HIV-1 infection in a subject) of a disclosed bispecific and / or single- domain antibody or multimer thereof or a nucleic acid encoding the bispecific and / or single- domain antibody or multimer thereof to a subject with or at risk of the HIV-1 infection. The methods can be used pre-exposure (for example, to prevent HIV-1 infection), in post- exposure prophylaxis, or for treatment of a subject with an HIV-1 infection. In some examples, the bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule can be used to eliminate or reduce the viral reservoir of HIV-1 in a subject.4239-111089-02HIV-1 infection does not need to be completely inhibited for the method to be effective. For example, the method can decrease HIV-1 infection by at least 10%, at least 20%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or even at least 100% (elimination of detectable HIV-1 infected cells), as compared to HIV-1 infection in the absence of the treatment. In some implementations, the method results in a reduction of HIV-1 replication in the subject. HIV-1 replication does not need to be completely eliminated for the method to be effective. For example, the method can reduce HIV-1 replication in the subject by at least 10%, at least 20%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, or even at least 100% (elimination of detectable HIV-1 replication), as compared to HIV-1 replication in the absence of the treatment. In some implementations, administration of an effective amount of a disclosed bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule inhibits the establishment of HIV-1 infection and / or subsequent HIV-1 progression in a subject, which can encompass any statistically significant reduction in HIV-1 activity or symptoms of HIV-1 infection in the subject. In one implementation, administration of a disclosed bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule results in a reduction in the establishment of HIV-1 infection and / or reducing subsequent HIV-1 disease progression in a subject. A reduction in the establishment of HIV-1 infection and / or a reduction in subsequent HIV-1 disease progression encompass any statistically significant reduction in HIV-1 activity. In some implementations, methods are disclosed for treating a subject with an HIV-1 infection. These methods include administering to the subject a effective amount of a disclosed bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule to preventing or treating the HIV-1 infection. Studies have shown that the rate of HIV-1 transmission from mother to infant is reduced significantly when zidovudine is administered to HIV-infected women during pregnancy and delivery and to the offspring after birth (Connor et al., 1994 Pediatr Infect Dis J 14: 536-541). The present disclosure provides bispecific and / or single-domain antibodies or multimers thereof and nucleic acid molecules that are of use in decreasing HIV-transmission from mother to infant. In some examples, an effective amount of a disclosed bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule encoding the bispecific and / or single-domain antibody or multimer thereof is administered to a pregnant subject in order to prevent transmission of HIV-1, or decrease the risk of transmission of4239-111089-02HIV-1, from a mother to an infant. In some examples, an effective amount of the bispecific and / or single-domain antibody or multimer thereof or nucleic acid encoding the bispecific and / or single-domain antibody or multimer thereof is administered to mother and / or to the child at childbirth. In other examples, an effective amount of the bispecific and / or single- domain antibody or multimer thereof or nucleic acid molecule encoding the bispecific and / or single-domain antibody or multimer thereof is administered to the mother and / or infant prior to breast feeding in order to prevent viral transmission to the infant or decrease the risk of viral transmission to the infant. For any application, the bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule can be combined with anti-retroviral therapy. Antiretroviral drugs are broadly classified by the phase of the retrovirus life-cycle that the drug inhibits. The disclosed bispecific and / or single-domain antibody or multimer thereof can be administered in conjunction with nucleoside analog reverse-transcriptase inhibitors (such as zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine, entecavir, and apricitabine), nucleotide reverse transcriptase inhibitors (such as tenofovir and adefovir), non- nucleoside reverse transcriptase inhibitors (such as efavirenz, nevirapine, delavirdine, etravirine, and rilpivirine), protease inhibitors (such as saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, fosamprenavir, atazanavir, tipranavir, and darunavir), entry or fusion inhibitors (such as maraviroc and enfuvirtide), maturation inhibitors, (such as bevirimat and vivecon), or a broad spectrum inhibitors, such as natural antivirals. In some examples, a disclosed bispecific and / or single-domain antibody or multimer thereof or nucleic acid such is administered in conjunction with IL-15, or conjugated to IL-15. Studies have shown that cocktails of HIV-1 neutralizing antibodies that target different epitopes of gp120 can treat macaques chronically infected with SHIV (Shingai et al., Nature, 503, 277-280, 2013; and Barouch et al., Nature, 503, 224-228, 2013). Accordingly, in some examples, a subject is further administered one or more additional antibodies that bind HIV-1 Env (e.g., that bind to gp120 or gp41), and that can neutralize HIV-1. The additional antibodies can be administrated before, during, or after administration of the novel antibodies disclosed herein. In some implementations, the additional antibody can be an antibody that specifically binds to an epitope on HIV-1 Env such as the membrane- proximal external region (e.g., 10E8 antibody), the V1 / V2 domain (e.g., PG9 antibody, CAP256-VRC26 ), or the V3 loop (e.g., 10-1074, PGT 121, or PGT128 antibody), or those that bind both gp120 and gp41 subunits (eg.35O22, PGT151, or 8ANC195). Antibodies that specifically bind to these regions and neutralizing HIV-1 infection are known to the person of4239-111089-02ordinary skill in the art. Non-limiting examples can be found, for example, in PCT Pub. No. WO 2011 / 038290, WO / 2013 / 086533, WO / 2013 / 090644, WO / 2012 / 158948. Antibodies are typically administered by intravenous infusion. Doses of the bispecific and / or single-domain antibody or multimer thereof vary, but generally range between about 0.5 mg / kg to about 50 mg / kg, such as a dose of about 1 mg / kg, about 5 mg / kg, about 10 mg / kg, about 20 mg / kg, about 30 mg / kg, about 40 mg / kg, or about 50 mg / kg. In some implementations, the dose of the bispecific antibody can be from about 0.5 mg / kg to about 5 mg / kg, such as a dose of about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg or about 5 mg / kg. The bispecific and / or single-domain antibody or multimer thereof is administered according to a dosing schedule determined by a medical practitioner. In some examples, the bispecific and / or single-domain antibody or multimer thereof is administered weekly, every two weeks, every three weeks or every four weeks. In some examples, a subject is administered DNA or RNA encoding a disclosed bispecific and / or single-domain antibody or multimer thereof to provide in vivo antibody production, for example using the cellular machinery of the subject. Administration of nucleic acid constructs is known in the art and taught, for example, in U.S. Patent No. 5,643,578, U.S. Patent No.5,593,972 and U.S. Patent No.5,817,637. U.S. Patent No. 5,880,103 describes several methods of delivery of nucleic acids encoding proteins to an organism. One approach to administration of nucleic acids is direct administration with plasmid DNA, such as with a mammalian expression plasmid. The nucleotide sequence encoding the disclosed bispecific and / or single-domain antibody or multimer thereof can be placed under the control of a promoter to increase expression. The methods include liposomal delivery of the nucleic acids. Such methods can be applied to the production of a bispecific and / or single-domain antibody or multimer thereof. In some implementations, a disclosed bispecific and / or single-domain antibody or multimer thereof is expressed in a subject using the pVRC8400 vector (described in Barouch et al., J. Virol., 79(14), 8828-8834, 2005). In several implementations, a subject (such as a human subject at risk of HIV-1 infection) can be administered an effective amount of an AAV viral vector that includes one or more nucleic acid molecules encoding a disclosed bispecific and / or single-domain antibody or multimer thereof. The AAV viral vector is designed for expression of the nucleic acid molecules encoding a disclosed bispecific and / or single-domain antibody or multimer thereof, and administration of the effective amount of the AAV viral vector to the subject leads to expression of an effective amount of the bispecific and / or single-domain antibody or multimer thereof in the subject. Non-limiting examples of AAV viral vectors that can be4239-111089-02used to express a disclosed antibody in a subject include those provided in Johnson et al., Nat. Med., 15(8):901-906, 2009 and Gardner et al., Nature, 519(7541):87-91, 2015. In one implementation, a nucleic acid encoding a disclosed bispecific and / or single- domain antibody or multimer thereof is introduced directly into tissue. For example, the nucleic acid can be loaded onto gold microspheres by standard methods and introduced into the skin by a device such as Bio-Rad’s HELIOS^ Gene Gun. The nucleic acids can be “naked,” consisting of plasmids under control of a strong promoter. Typically, the DNA is injected into muscle, although it can also be injected directly into other sites. Dosages for injection are usually around 0.5 µg / kg to about 50 mg / kg, and typically are about 0.005 mg / kg to about 5 mg / kg (see, e.g., U.S. Patent No.5,589,466). Single or multiple administrations of a composition including a disclosed bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule can be administered depending on the dosage and frequency as required and tolerated by the patient. The dosage can be administered once, but may be applied periodically until either a desired result is achieved or until side effects warrant discontinuation of therapy. Generally, the dose is sufficient to inhibit HIV-1 infection without producing unacceptable toxicity to the patient. Data obtained from cell culture assays and animal studies can be used to formulate a range of dosage for use in humans. The dosage normally lies within a range of circulating concentrations that include the ED50, with little or minimal toxicity. The dosage can vary within this range depending upon the dosage form employed and the route of administration utilized. The effective dose can be determined from cell culture assays and animal studies. The bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule encoding the bispecific and / or single-domain antibody or multimer thereof, or a composition including such molecules, can be administered to subjects in various ways, including local and systemic administration, such as, e.g., by injection subcutaneously, intravenously, intra-arterially, intraperitoneally, intramuscularly, intradermally, or intrathecally. In an implementation, the bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule, or a composition including such molecules, is administered by a single subcutaneous, intravenous, intra-arterial, intraperitoneal, intramuscular, intradermal or intrathecal injection once a day. The bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule, or a composition including such molecules, can also be administered by direct injection at or near the site of disease. A further method of administration is by osmotic pump (e.g., an Alzet pump) or mini-pump (e.g., an Alzet mini-4239-111089-02osmotic pump), which allows for controlled, continuous and / or slow-release delivery of the bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule or a composition including such molecules, over a pre-determined period. The osmotic pump or mini-pump can be implanted subcutaneously, or near a target site. 2. Compositions Compositions are provided that include the bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule that are disclosed herein in a carrier. The compositions are useful, for example, for the inhibition or detection of an HIV-1 infection. The compositions can be prepared in unit dosage forms for administration to a subject. The amount and timing of administration are at the discretion of the administering physician to achieve the desired purposes. The bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule can be formulated for systemic or local administration. In one example, the bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule is formulated for parenteral administration, such as intravenous administration. In some implementations, the bispecific and / or single-domain antibody or multimer thereof in the composition is at least 70% (such as at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99%) pure. In some implementations, the composition contains less than 10% (such as less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, or even less) of macromolecular contaminants, such as other mammalian (e.g., human) proteins. The compositions for administration can include a solution of the bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule dissolved in a pharmaceutically acceptable carrier, such as an aqueous carrier. A variety of aqueous carriers can be used, for example, buffered saline and the like. These solutions are sterile and generally free of undesirable matter. These compositions may be sterilized by conventional, well-known sterilization techniques. The compositions may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions such as pH adjusting and buffering agents, toxicity adjusting agents and the like, for example, sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate and the like. The concentration of bispecific and / or single-domain antibody or multimer thereof in these formulations can vary, and will be selected primarily based on fluid volumes, viscosities,4239-111089-02body weight and the like in accordance with the particular mode of administration selected and the subject’s needs. A typical composition for intravenous administration includes about 0.01 to about 30 mg / kg of bispecific and / or single-domain antibody or multimer thereof per subject per day. Actual methods for preparing administrable compositions are known and are described in more detail in such publications as Remington: The Science and Practice of Pharmacy, 22nded., London, UK: Pharmaceutical Press, 2013. In some implementations, the composition can be a liquid formulation including one or more bispecific and / or single-domain antibody or multimer thereof in a concentration range from about 0.1 mg / ml to about 20 mg / ml, or from about 0.5 mg / ml to about 20 mg / ml, or from about 1 mg / ml to about 20 mg / ml, or from about 0.1 mg / ml to about 10 mg / ml, or from about 0.5 mg / ml to about 10 mg / ml, or from about 1 mg / ml to about 10 mg / ml. The bispecific and / or single-domain antibody or multimer thereof or the nucleic acid molecule can be provided in lyophilized form and rehydrated with sterile water before administration, although they are also provided in sterile solutions of known concentration. The bispecific and / or single-domain antibody or multimer thereof or nucleic acid molecule solution can then be added to an infusion bag containing 0.9% sodium chloride, USP, and typically administered at a dosage of from 0.5 to 15 mg / kg of body weight. Considerable experience is available in the art in the administration of antibody drugs, which have been marketed in the U.S. since the approval of Rituximab in 1997. The bispecific and / or single- domain antibody or multimer thereof or the nucleic acid molecule can be administered by slow infusion, rather than in an intravenous push or bolus. In one example, a higher loading dose is administered, with subsequent, maintenance doses being administered at a lower level. For example, an initial loading dose of 4 mg / kg may be infused over a period of some 90 minutes, followed by weekly maintenance doses for 4-8 weeks of 2 mg / kg infused over a 30-minute period if the previous dose was well tolerated. Controlled-release parenteral formulations can be made as implants, oily injections, or as particulate systems. For a broad overview of protein delivery systems see, e.g., Banga, Therapeutic Peptides and Proteins: Formulation, Processing, and Delivery Systems, 3rdedition, CRC Press, 2015. Particulate systems include microspheres, microparticles, microcapsules, nanocapsules, nanospheres, and nanoparticles. Microcapsules contain the active protein agent, such as a cytotoxin or a drug, as a central core. In microspheres, the active protein agent is dispersed throughout the particle. Particles, microspheres, and microcapsules smaller than about 1 µm are generally referred to as nanoparticles,4239-111089-02nanospheres, and nanocapsules, respectively. Capillaries have a diameter of approximately 5 µm so that only nanoparticles are administered intravenously. Microparticles are typically around 100 µm in diameter and are administered subcutaneously or intramuscularly. Polymers can be used for ion-controlled release of the antibody compositions disclosed herein. Any suitable polymer may be used, such as a degradable or nondegradable polymeric matrix designed for use in controlled drug delivery. Alternatively, hydroxyapatite has been used as a microcarrier for controlled release of proteins. In yet another aspect, liposomes are used for controlled release as well as drug targeting of the lipid-capsulated drug. 3. Methods of detection and diagnosis Methods are also provided for the detection of the presence of HIV-1 Env in vitro or in vivo. In one example, the presence of HIV-1 Env is detected in a biological sample from a subject, and can be used to identify a subject with HIV-1 infection. The sample can be any sample, including, but not limited to, tissue from biopsies, autopsies and pathology specimens. Biological samples also include sections of tissues, for example, frozen sections taken for histological purposes. Biological samples further include body fluids, such as blood, serum, plasma, sputum, spinal fluid or urine. The method of detection includes contacting a cell or sample, with a bispecific and / or single-domain antibody or multimer thereof as provided herein that specifically binds to HIV-1 Env or conjugate thereof (e.g. a conjugate including a detectable marker) under conditions sufficient to form an immune complex, and detecting the immune complex (e.g., by detecting a detectable marker). In one implementation, the bispecific and / or single-domain antibody or multimer thereof is directly labeled with a detectable marker. In another implementation, the bispecific and / or single-domain antibody or multimer thereof that binds HIV-1 Env (the primary antibody) is unlabeled and a secondary antibody or other molecule that can bind the primary antibody is utilized for detection. The secondary antibody is chosen that is able to specifically bind the specific species and class of the first antibody. For example, if the first antibody is a human IgG, then the secondary antibody may be an anti-human-IgG. Other molecules that can bind to antibodies include, without limitation, Protein A and Protein G, both of which are available commercially. Suitable labels for the bispecific and / or single- domain antibody or multimer thereof or secondary antibody are known and described above,4239-111089-02and include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, magnetic agents and radioactive materials. In some implementations, the disclosed bispecific and / or single-domain antibody or multimer thereof is used to test vaccines. For example, to test if a vaccine composition including an HIV-1 Env or fragment thereof assumes a conformation including the epitope(s) of a disclosed bispecific and / or single-domain antibody or multimer thereof. Thus, provided herein is a method for testing a vaccine, wherein the method includes contacting a sample containing the vaccine, such as an HIV-1 Env immunogen, with a disclosed bispecific and / or single-domain antibody or multimer thereof under conditions sufficient for formation of an immune complex, and detecting the immune complex, to detect the vaccine, such as an HIV- 1 Env immunogen including the epitope, in the sample. In one example, the detection of the immune complex in the sample indicates that the vaccine component, such as an HIV-1 Env immunogen, assumes a conformation capable of binding the bispecific and / or single-domain antibody or multimer thereof. III. EXAMPLES The following examples are provided to illustrate particular features of certain implementations, but the scope of the claims should not be limited to those features exemplified. Example 1 Materials and Methods Expression and purification of BG505 DS-SOSIP and related proteins BG505 DS-SOSIP protein was expressed and purified as previously described (Kwon et al., Nat Struct Mol Biol 22:522-531, 2015). Glycan-base (BG505 DS-SOSIP.4mut_N502- 660) and CD4bs knockout (KO 4115) constructs of BG505 were expressed with an N- terminal scFc tag, separated by an HRV-3C cleavage site. The plasmids were transfected into FreeStyleTM293-F cells (Thermo) and protein was expressed for 6 days at 37°C. The cell supernatant was collected by centrifugation and applied to Protein A resin (Cytivia), after which the HIV Env was liberated by cleavage with HRV-3C. The flowthrough was collected and applied to a Superdex® S-200 gel filtration column, after which the protein was concentrated to 1mg / ml, flash frozen with 10% glycerol, and stored at -80°C until use. His- tagged RSC3 was first purified from day-5 supernatant of transiently transfected 293F cells4239-111089-02using Ni-NTA-resin (Qiagen) and monomeric RSC3 was further purified through a HiLoad 16 / 600 Superdex200 sizing column (Cytiva) on an AKTA PureTMFPLC system. HIV-1 fusion peptide (FP8) was synthesized and biotinylated by GenScript. Llama immunizations and nanobody phage library construction Llama immunization procedures were performed by following Capralogics Inc. ACUC protocol. One llama (Capralogics) was immunized subcutaneously with 1 mg of recombinant BG505 DS-SOSIP protein in the presence of CFA at day 0, and boost immunized with 0.5 mg of BG505 DS-SOSIP protein in the presence of IFA on day 21, 42, 63, 84, 105, 126, 147, 168, 189, 210, 231, and 257, respectively. Test blood / serum samples were taken on day 0, 52, 73, 94, 115, 136, 157, 178, 199, 220, 241 and 271 for antibody- antigen binding tests and neutralization tests.300 ml of whole blood were collected on day 188 and 271, and peripheral blood mononuclear cells (PBMCs) were isolated and used for nanobody phage libraries construction as previously described (Xu et al., Nature 595:278- 282, 2021). Phage screening for HIV-1 Env binding nanobodies Four HIV-1 Env related proteins were used for phage screening: Env trimer (BG505 DS-SOSIP), Glycan base trimer (BG505 DS-SOSIP.4mut_N502-660), RSC3 and biotinylated Fusion peptide. For Env trimer, glycan base trimer or RSC3 screening, three wells of MaxiSorpTM96-well plate (Thermo Fisher Scientific) were first coated with lectin (EMD Millipore, L8275, 100 μg / ml in PBS) at 4°C overnight, washed with PBS with 0.1% Tween-20 three times and blocked with 5% non-fat milk in PBS at room temperature for 1 hour, then coated with 50 μl of 100 μg / ml proteins at room temperature for 2 hours. One well without target protein was included as non-coated control. For biotinylated FP8 screening, two wells of Streptavidin-coated plates (Thermo Fisher Scientific) were coated with 50 μl of FP8 (100 μg / ml in PBS) at 4°C overnight, washed and blocked with non-fat milk. Another well with 50 μl of PBS was used as non-coated control. Nanobody phages were added to wells and screened as previously described (Xu et al., Nature 595:278-282, 2021). Enzyme-linked immunosorbent assay After one or two rounds of selection, TG-1 cells from sub libraries were plated and colonies were picked to prepare periplasmic extracts containing crude nanobodies. Serum samples from different time points and nanobody candidates were tested for their binding to4239-111089-02individual target proteins by enzyme-linked immunosorbent assay (ELISA) as previously described (Xu et al., Nature 595:278-282, 2021). In brief, glycan proteins were coated onto Maxisorp plates indirectly through lectin and biotinylated FP8 was coated to streptavidin coated plates. Plates were washed and blocked, and then 100 μl of diluted serum samples or undiluted nanobody-containing supernatant were added and incubated for 2 hours at room temperature. Horse radish peroxidase (HRP) conjugated goat anti-alpaca VHH domain specific antibody (Jackson ImmunoResearch) and tetramethylbenzidine (TMB) (Thermo Fisher Scientific) were used for developing ELISA signals, which were measured with Synergy microplate reader (BioTek Gen5). Expression and purification of nanobodies and Fc conjugated nanobody variants Nanobodies were expressed and purified as previously described (Xu et al., Nature 595:278-282, 2021). In brief, phagemids of lead nanobodies were extracted from TG-1 cells and transformed into WK6 cells (ATCC). WK6 cells were cultured in 2YT medium and induced by IPTG for nanobody expression. Cells were pelleted and treated with polymyxin B to release nanobodies from periplasmic region. Nanobodies in the supernatant were purified using CapturemTMHis-tagged purification kit (Takara) or cOmpleteTMHis-tag purification resin (Roche), dialyzed and filtered sterile before being used for downstream assays. Monomeric or multimeric nanobody sequences were fused to the Fc region of human IgG1 through llama IgG2a hinge and cloned into the pVRC8400 vector. In multimeric form, nanobody units were connected through (GGGGS)×3 flexible linkers. The Fc fusion constructs were expressed in Expi293 cells and antibodies in the supernatant were purified using protein A, concentrated, dialyzed and the filtered sterile. HIV neutralization test Neutralization was measured using single-round-of-infection HIV-1 Env- pseudoviruses and TZM-bl target cells, as described previously (Sarzotti-Kelsoe et al., J Immunol Methods 409:131-146, 2014). Neutralization curves were fit by nonlinear regression using a 5-parameter hill slope equation. The neutralization titers were calculated as a reduction in luminescence units compared with control wells and reported as 50% or 80% inhibitory concentration (IC50 or IC80) in micrograms per milliliter.4239-111089-02Biolayer Interferometry Assay for epitope mapping A FortéBio 96-Channel Ultra High Throughput Octet® System was used to map the binding epitopes of his-tagged nanobodies. Assays were performed at 30°C in tilted black 384-well plates (Geiger Bio-One) in PBS + 0.02% Tween20, 0.1% BSA, 0.05% sodium azide with agitation set to 1,000 rpm. His-tagged nanobodies (50 µg / ml) were loaded onto Ni-NTA biosensors for 150 seconds. Bindings to HIV-1 Env were measured by dipping immobilized nanobodies into solutions of 200 nM BG505 DS-SOSIP without or with 720 nM Fabs of antibodies with known epitopes for 180 seconds. Fabs of antibodies VRC01, VRC34.01, 1E6, PGT145 and 10-1074 were used for competing the CD4bs, FP, Env-base, V2-apex and glycan V3 epitopes, respectively. Parallel correction to subtract systematic baseline drift was carried out by subtracting the measurements recorded for a loaded sensor dipped into buffer only control well. Degree of competition was calculated as (ratio of responses between BG505 DS-SOSIP in the presence of blocking Fab and BG505 DS-SOSIP alone)*100% and defined as three categories: complete (<30%), partial (30-60%) and slight (60-80%). Negative-staining electron microscopy analysis Samples used for negative-stain electron microscopy were diluted with a buffer containing 20 mM HEPES, pH 7.0, and 150 mM NaCl, adsorbed to a freshly glow- discharged carbon-film grid, washed with the above buffer, and stained with 0.7% uranyl formate. Images were collected at a magnification of 100,000 semi-automatically using SerialEM (Mastronarde et al., J Struct Biol 152:36-51, 2005) on a FEI Tecnai T20 microscope operating at 200 kV and equipped with a 2k x 2k Eagle CCD camera. The pixel size was 0.22 nm / px. Particles were picked manually and using the swarm mode in e2boxer from the EMAN2 software package (Tang et al., J Struct Biol 157:38-46, 2007). Reference- free 2D classification was performed using EMAN2 and SPIDER (Shaikh et al., Nat Protoc 3:1941-1974, 2008). Cryo-EM data collection, processing and model refinement Cryo-EM specimens were prepared by vitrification using a ThermoFisher Scientific VitrobotTMMark IV plunger. QuantifoilTMR 2 / 2 gold grids were glow-discharged using a PELCO easiGlowTMglow-discharger (air pressure: 0.39 mBar, current: 20 mA, duration: 30 s) immediately before use. Data was collected using SerialEM ( Mastronarde et al., J Struct Biol 152:36-51, 2005) with a ThermoFisher Titan Krios G1 electron microscope equipped4239-111089-02with a Gatan K2 Summit® direct electron detector operating in the counting mode (Table S1). Neutralization fingerprint analysis The neutralization fingerprints of day 188 and day 271 serum samples, defined as the potency pattern with which the sera neutralize a set of 60 HIV-1 strains, were analyze and compared as described previously (Georgiev et al., Science 340: 751-756, 2013). Nanobody lineage analysis Nucleotide sequences were submitted to IMGT Vquest server to assign the germline gene (https: / / www.imgt.org / IMGT_vquest / input). The phylogenetic trees were prepared by gctree with default parameters (DeWitt et al., Mol Biol Evol 35:1253-1265, 2018). Pharmacokinetic study in human neonatal Fc receptor-Fc (FcRn-Fc) transgenic mice Human FcRn-Fc transgenic mice (FcRn- / - hFcRn-Fc Tg mice, JAX stock # 029686, The Jackson Laboratory) were used to assess the pharmacokinetics of selected antibodies. Each animal was infused intravenously with 5 mg mAb / kg of body weight. Whole blood samples were collected at day 1, 2, 5, 7, 9, 14, 21, 28, 35, 42, 49 and 56. Serum mAb levels were measured by ELISA using anti-idiotypic antibody to CAP256 or BG505 DS-SOSIP trimer as described previously (Rudicell et al., J Virol 88:12669-12682, 2014). All mice were bred and maintained under pathogen-free conditions at the American Association for the Accreditation of Laboratory Animal Care-accredited Animal Facility at the National Institute of Allergy and Infectious Diseases and housed in accordance with the procedures outlined in the Guide for the Care and Use of Laboratory Animals. All the mice were between 6 and 13 weeks of age. The study protocol was evaluated and approved by the National Institutes of Health’s Animal Care and Use Committee (ASP VRC-20-893). Predicting Nanobody Neutralization against 208 HIV-1 Isolates Using our measured neutralization for bispecific antibodies against 80 HIV-1 isolates, it was extrapolated how these antibodies-of-interest would neutralize a larger panel of 208- isolates. Briefly, neutralization measurements from 80 reference monoclonal antibodies measured against the 208 isolates were combined. A matrix completion via nuclear norm minimization, which finds linear combinations of the reference antibodies that match the neutralization from the antibodies-of-interest and uses these linear combinations to infer the4239-111089-02remaining measurements, was then applied (Einav et al., Cell Syst 13:561-573 e565, 2022). To assess prediction error, 10% of available measurements was withheld and matrix completion was applied to compare the predicted-vs-measured values. The error of these predictions was 4-fold (i.e., a predicted IC80=0.4μg / mL should lie between 0.4 / 4=0.1μg / mL and 0.4×4=1.6μg / mL), far smaller than 107-fold range of the neutralization data. As done previously, IC80s were inverted and logged (IC80→ log10[1 / IC80]) prior to matrix completion and then reverted after matrix completion (Einav et al., Cell Syst 13:561-573 e565, 2022). Inverting ensures that the smallest values representing the strongest responses are predicted more accurately than weak responses. Log transformation prevents strong neutralization measurements from overpowering the predictions. Each reference antibody had at least 40 concrete measurements against the 80-isolate panel (i.e., ignoring bounded values such as IC80>100μg / mL) to enable comparison with the antibodies-of-interest. For each antibody-of- interest, the fraction of the 208-isolate panel that it neutralized with an IC80<50μg / mL was computed. To account for the 4-fold prediction error, several thousand simulations were run where every predicted IC80 was multiplied by a factor between 1 / 4 and 4 (equally sampled in a log-scale), counted the number of IC80s<50μg / mL, and fit the resulting distribution. Autoreactivity The autoreactivity of the antibodies was assessed using the ANA Hep-2 Test System (ZEUS Scientific, Cat. No: FA2400EB) and anticardiolipin ELISA kit (Inova Diagnostics Cat. No.: 708625). Briefly, to evaluate the binding of the antibodies to HEp-2 cells, all the antibodies were tested at 25 and 50 μg / ml in PBS buffer following the instructions from the manufacturer of the ANA Hep-2 Test System. The VRC01LS, 4E10, VRC07-523-LS, and VRC07-G54W antibodies were used as controls. Slides were imaged on a Nikon Eclipse Ts2R microscope with a 20 × objective lens for 500 ms. The fluorescent signals of the control antibodies at 25 ug / ml were scored as 0, 1, 2, and 3, respectively. The fluorescent signals of the test antibodies were estimated visually in comparison to the control ones. Scores over 1 at 25 μg / ml were defined as autoreactive, and between 0 and 1 as mildly autoreactive. For the cardiolipin ELISA, all the antibodies were tested at 100 μg / ml, followed by a 3-fold serial dilution. IgG phospholipid (GPL) units were derived from the standard curve. A GPL score below 20 was considered as not reactive, and between 20 and 80 as low positive and greater than 80 as high positive. The reported results are representative of two independent experiments.4239-111089-02Example 2 BG505 DS-SOSIP immunized llama develops broadly neutralizing serum responses To explore the anti-HIV potential of nanobodies, a llama was immunized with prefusion-stabilized HIV-1 Env trimer BG505 DS-SOSIP and broad HIV-1 neutralizing nanobodies were isolated. The llama was immunized 13 times (FIG.1A) and monitored for serum antibody response against multiple HIV Env probes over a course of 271 days (FIG. 1B). The immunization quickly induced strong sera titer against BG505 DS-SOSIP itself, as well as its CD4bs epitope knocked out version with slightly weaker signal, indicating the existence of CD4bs directed response on BG505 DS-SOSIP. Antibody responses were weaker against glycan base covered BG505 DS-SOSIP at early time points, suggesting most of the early immune response to be directed to the exposed base region of the soluble HIV-1 Env trimer. Starting from day ~115, stronger response developed against the glycan-base covered Env trimer and Env of ConC strain, suggestive of cross clade recognition. Interestingly, epitope-specific antibody response, such as CD4bs-specific probe RSC3 (Wu et al., Science 329:856-861, 2010) and fusion peptide-specific probe FP8 (Xu et al., Nat Med 24:857-867, 2018), were not detected until later time points in the immunization. Consistent with mainly Env trimer protein-base targeting immune response observed by ELISA at days 52, 73, and 94, the serum neutralizing potency and breadth on a 14-strain panel was weak for these three time points, and the serum neutralization response improved substantially starting around day 115 (Fig.1C). Neutralization breadth reached 100% by day 178, and the potency against the 14 strains kept increasing until the experiment was terminated on day 271. The neutralization activity of sera from days 178 and 271 on an unbiased 50-strain panel was further tested (Doria-Rose et al., PLoS Pathog 13:e1006148, 2017). Data on the non-overlapping 60-stains from the two panels showed that the neutralization breadth increased from 77% on day 178 to 88% by day 271, and neutralization titer (geometric mean ID50) increased from 357 on day 178 to 1032 on day 271 (FIGs.1D & 9A). Neutralization fingerprinting analysis (Georgiev et al., Science 340:751-756, 2013) predicted that majority of neutralization was VRC01-like (66%~70%), indicating CD4bs- directed antibody response to dominate (FIG.9B). These results demonstrated that BG505 DS-SOSIP can elicit broad and potent anti-HIV-1 antibody response in llama in a short period of time.4239-111089-02Example 3 Isolation and testing of HIV-1 broadly neutralizing nanobodies To isolate monoclonal neutralizing nanobodies, a nanobody phage library was constructed from PBMCs of whole blood on day 188, 10 days after serum neutralizing breadth on a 14-strain panel first reached 100% (FIG.2A). Four protein / peptide probes were used for nanobody screening, Env Trimer (BG505 DS-SOSIP), Fusion peptide, Glycan-base trimer (BG505 DS-SOSIP.4mut_N502-660) and RSC3, and nanobodies identified from these probes were named as a single letter (underlined in probe name) followed by a number. In total 151 nanobodies with unique sequences were identified and expressed for further analysis. Binding epitopes on HIV-1 Env for these nanobodies were mapped by a competition biolayer interferometry assay using Fabs of five antibodies with known epitopes: VRC01 (Wu et al., Science 329:856-861, 2010) for the CD4bs, VRC34.01 (Kong et al., Science 352:828-833, 2016) for the FP epitope, 1E6 (Cottrell et al., PLoS Pathog 16:e1008753, 2020) for the Env-base, PGT145 (Lee et al., Immunity 46:690-702, 2017) for the V2-apex, and 10- 1074 (Mouguet et al., Proc Natl Acad Sci U S A 109:E3268-3277, 2012) for the V3 glycan (FIGs.2B & 10A). Of the 69 nanobodies identified by Env trimer probe, 4 competed with VRC34.01, 19 competed with 1E6, and 46 did not compete with any of the five antibodies; of the 9 nanobodies identified by FP probe, 7 competed with VRC34.01, 2 competed with 1E6; of the 45 nanobodies identified by Glycan-base trimer, 2 competed with VRC01, 17 competed with VRC34.01, 26 competed with 1E6. Interestingly, all of the 28 nanobodies identified by RSC3 probe competed with VRC01, indicating CD4bs targeting. More importantly, the phylogenetic tree of the 151 Env-binding nanobodies showed that VRC01- competing nanobodies formed a cluster, and VRC34.01-competing nanobodies formed another cluster (FIGs.2C-2D). From the phylogenetic tree, 30 representative nanobodies were selected (10 VRC34.01- or 1E6-competing, 14 non-competing, and 6 VRC01- competing), and their neutralization activity was tested on the same 14-strain panel used for the initial serum test. None of the 10 VRC34.01- or 1E6-competing nanobodies neutralized any strain (non-neutralizers), and 1 of the 14 non-competing nanobodies neutralized 2 strains (weak neutralizers) (FIGs.2C & 10B). However, all 6 VRC01-competing nanobodies neutralized well, with various potency and breadth (FIG.2D). Specifically, 4 broad neutralizers were identified. G36 neutralized all of the 14 strains with a geometric mean IC50 of 0.088 µg / ml; R11, R21 and R25 neutralized over 11 strains; and two moderate neutralizers, G42 and R18, neutralized 8 strains.4239-111089-02Another nanobody phage library was constructed from day 271 PBMCs and the same screening was carried out to identify 117 nanobodies. After comparing their CDR sequences with nanobodies identified from day 188 library, 17 representative nanobodies were selected for 5-strain panel neutralization assessment (FIGs.2E & 10C). Of those, R27, E46 and G1 neutralized 5, 2, and 4 strains, respectively. Three lineages of HIV-1 neutralizing nanobodies To obtain a more comprehensive analysis of potentially good neutralizing nanobodies, phylogenetic trees were plotted for 42 nanobodies from day 188 and day 271 that belonged to the same lineages of the 4 broad neutralizers above, G36, R11, R21, and R25 from day 188 (FIG.3A). D188_G36 and D271_G1 belonged to the same lineage; R11 lineage included 13 nanobodies from day 188 and 12 nanobodies from day 271, including D271_R27; R21 and R25 belonged to one lineage together with 7 other nanobodies from day 188 and 6 nanobodies from day 271. These 42 nanobodies showed various neutralizing breadth and potency on a 10-strain panel, and 6 of them showed 90% breadth (FIG.3B); these 6 were tested on an additional 15-strain panel (FIG.3C). The broadest nanobody D188_G36 (21 / 25, hereafter referred to as G36) and the most potent nanobody D271_R27 (geometric mean IC50: 0.101 µg / ml, hereafter referred to as R27) were selected for further characterization. Example 4 Improve neutralization potency and breadth by Fc conjugation and multimerization As multimerization and Fc conjugation can increase the affinity of nanobodies and their neutralization potency (Xu et al., Nature 595:278-282, 2021), G36 and R27 were further engineered with this modification; the 5-strain panel test revealed the potency of both nanobodies to be improved by Fc conjugation (bivalent), and R27 was further improved by combining tandem multimerization and Fc conjugation (nanobody x3-IgG2a) (FIGs.4A-4B). The amino acid sequences of G36x3-IgG2a and R27x3-IgG2a are provided herein as SEQ ID NOs: 52 and 53, respectively. The same pattern was seen for several other nanobodies, and most interestingly, three VRC34.1-competing nanobodies, F7, G25 and G39, could neutralize after Fc conjugation and / or multimerization (FIG.11A). The improvement of both breadth and potency of G36x3-IgG2a and R27x3-IgG2a over their monomeric (single-domain) forms were further confirmed on a 25-vrius panel (FIGs.4C & 11B), with both reaching over 96% breadth. The standard 208-vrius panel assay were then performed on the two antibodies in4239-111089-02x3-IgG2a format, and results showed that both neutralized 96% at geometric mean IC50of 0.1 and 0.016 µg / ml for G36x3-IgG2a and R27x3-IgG2a, respectively (FIG.4D). The breadth of 92% and 87% (with IC80<50 µg / ml) and geometric mean IC 80 of 0.314 and 0.033 µg / ml for G36x3-IgG2a and R27x3-IgG2a, respectively (FIGs.4E and 11C), rank among the best reported HIV-1 broadly neutralizing antibodies. Example 5 Structural basis for the broad HIV-1 neutralization of R27 and G36 To elucidate the mechanism by which the potent and broad llama nanobodies recognize Env trimer, the structures of R27 and G36 in complex with BG505 DS-SOSIP were determined by cryo-EM. The cryo-EM reconstruction map of R27 in complex with BG505 DS-SOSIP was obtained at 3.6 Å nominal resolution from 315,969 particles (FIGs. 5A, 12A-12E & 18). The refined structural model revealed binding of three copies of R27, each to a protomer of the Env trimer, at the CD4bs. Cryo-EM reconstruction of G36 in complex with BG505 DS-SOSIP was achieved at 3.3 Å from 414,002 particles, and the refined structure revealed a binding mode of G36 similar to that of R27 (FIGs.5B, 13A-13E & 18). The epitope of R27 covered 715 Å2on one protomer with minor interaction of 21 Å2with a neighboring protomer (FIGs.5C &15A-15C). G36 epitope was slightly larger at 885 Å2on one protomer and 172 Å2on the neighboring protomer (FIGs.5C & 16A-16C). Both epitopes were at a similar location to that of J3 (McCoy et al., J Exp Med 209:1091-1103, 2012; Zhou et al., Structure 30:862-875 e864, 2022). Indeed, R27, G36, and J3, as well as the domain 1 of CD4, all bound at a similar location in the canyon between two gp120 subunits (FIG.5D). The approach angles of R27 and G36 were slightly different (FIG.5D). This and their different sequences resulted in some differences in paratope-epitope interactions between the two nanobody-Env trimer complexes. Both R27 and G36 made extensive interactions to the CD4-binding loop, loops D and V5 on the major binding gp120 protomer through residues in their CDR2 and CDR3 (FIGs.5E-5F, 15A-15C &16A-16C), typical for CD4BS-targeting antibodies. Moreover, G36 inserted Tyr99 to the hydrophobic “Phe43 pocket” of gp120 to mimic the CD4 Phe43-gp120 interaction (FIG.5G), similar to J3 which used Tyr99 (Zhou et al., Structure 30:862-875 e864, 2022; Zhou et al., Science 329:811-817, 2010). The mimicry of CD4 Phe43 was also observed in the human VRC01-class antibodies, such as N6 and VRC-PG20 (Huang et al., Immunity 45:1108-1121, 2016; Zhou et al., Immunity 39:245-258, 2013), which used Tyr54 or Trp54 to interact with the gp120 pocket,4239-111089-02demonstrating the ability of immune systems to take advantage of this site of vulnerability on HIV-1 Env trimers. Overall, R27 and G36 bound at the CD4bs, in the canyon between two gp120 subunits with quaternary interactions, mimicking CD4 binding. Example 6 Ultrapotent and broad HIV-1 neutralizing bispecific antibodies To further improve the potency and breadth, bispecific antibodies containing the CD4bs-targeting nanobodies G36 or R27 or variants thereof, were designed. The following table provides sequences for the bispecific antibodies: Bispecific antibody Light chain fused to VHH Heavy chain CAP256-G36 VRC26.25L-G36 CAP256V2LS H ) ) ) ) ) ) ) ) ) ) ) ) Briefly, the CD4bs-targeting nanobodies, G36 or R27 or variants or multimers thereof, were attached to the N-terminus of the light chain of a V2 apex-targeting broadly neutralizing antibody CAP256V2LS (FIG.6A), creating human-llama bispecific antibodies (see, e.g., Zhang et al., MAbs 15: 2165390, 2023). A 38-strain panel test showed that conjugating nanobody monomers (G36, R27, and J3) with CAP256LS improved neutralization potency over their triplet conjugation on human IgG1 Fc domain (x3-IgG2a4239-111089-02format described above) (FIG.6B). While CAP256L-G36x3LS was not better than CAP256L-G36LS, both CAP256L-R27x3LS and CAP256L-J3x3LS substantially improved neutralizing potency, with CAP256L-R27x3LS being the most potent (geometric mean IC50=0.004 µg / ml). CAP256L-G36x3LS and CAP256L-R27x3LS were then tested on an additional 42 viruses, and the overall 80-strain panel data showed that the two bispecific antibodies neutralized over 94% of cross-clade HIV-1 viruses ultrapotently, with 0.012 µg / ml and 0.003 µg / ml geometric mean IC50, respectively (FIG.6C). Indeed, estimating IC80neutralization on a 208-strain panel suggested the combined potency and breadth for CAP256L-R27x3 to exceed other published HIV-1 bNabs (FIGs.6D, 17A-17B), as well as the best multi-specific antibodies. Structural basis for the broad HIV-1 neutralization of CAP256L-R27x3LS A cryo-EM structure for CAP256L-R27 bound to BG505 DS-SOSIP revealed a single CAP256V2LS Fab to bind at the V2-apex and three copies of R27 each to bind to a CD4bs of the trimer (FIGs.7A-7B, 14A-14F & 18). Even though the cryo-EM density for the linker between R27 and CAP256 light chain was disordered, one of the bound R27s could be identified by its proximity to link with the light chain of CAP256 that bound to the V2-apex (FIGs.7A-7B), the other two R27s were from separate CAP256L-R27 molecules (FIG.14F). A cryo-EM structure for CAP256L-R27x3 bound to BG505 DS-SOSIP was not able to be captured due to antibody caused aggregation. Improved pharmacokinetics of CAP256L-R27x3LS The autoreactivity of R27 and its variants was then determined. While three control antibodies showed binding score of 1, 2, and 3, none of R27 or its variants showed binding to Hep-2 cells, indicating no antinuclear antibody (ANA) response. R27, R27-IgG2a and R27x3-IgG2a were negative in anti-Cardiolipin ELISA test, while CAP256L-R27LS and CAP256L-R27x3LS showed low autoreactivity, which is similar to CAP256.J3LS (FIG.8A). Analysis of the pharmacokinetics of the various forms of R27 revealed a very short half-live for R27x3-IgG2a-LS in human FcRn-Fc-KI mice, whereas the CAP256L-R27x3 half-life was just a little bit shorter than the parent CAP256V2LS (FIG.8B).4239-111089-02Discussion Multiple animals have evolved alternatives to the heavy-light antibody recognition utilized by the human immune system (McCoy et al., J Exp Med 209:1091-1103,2012; Xu et al., Nature 595:278-282, 2021; Sok et al., Nature 548:108-111, 2017; Weiss et al., Vaccines (Basel) 7:77, 2019), and these alternatives provide unique ways to bypass HIV’s glycan defenses. With cows, immunization with prefusion-closed Env trimer elicits broadly neutralizing antibodies, with cow-specific D-regions of up to 48 residues, extending from the body of the antibody to reach conserved elements of the CD4bs (Sok et al., Nature 548:108- 111, 2017). With llamas, immunization with gp140 elicited nanobodies such as J3, with VHH recognition enabled mimicry of CD4 (McCoy et al., J Exp Med 209:1091-1103,2012; Zhou et al., Structure 30:862-875 e864, 2022). Serum neutralization, however, from the gp140 immunized llamas was not broadly neutralizing. As shown here, immunizations of a llama with a prefusion-closed trimer initially yield only autologous neutralization, but after repeated immunizations develop into a broadly neutralizing response. Immunizations with the same immunogen in humans, two doses eight weeks apart, yield autologous neutralizing antibodies that target the fusion-peptide site of vulnerability (Houser et al., EClinicalMedicine 48, 101477, 2022; Wang et al., Cell Rep 42:112755, 2023). Antibodies from repeated llama immunizations responsible for the serum neutralization, however, mapped to the CD4bs, and CD4bs nanobodies with greater than 90% breadth and substantially higher potency than J3 were identified. Combination of these antibodies with the potent V2-directed antibody, CAP256V2LS, yielded bispecifics of even greater neutralization potency. The best of the bispecifics, CAP256L-R27x3LS, reached levels of potency that rivaled the best multi-specific antibodies developed thus far. CAP256L-R27x3LS neutralized over 95% of an 80-strain panel with a geometric mean IC80 of 0.008 mg / ml, and computational extrapolation predicted neutralization of the 208-strain panel with a breadth of 97% and a geometric mean IC80 of 0.017 mg / ml. In comparison, the other reported bispecific antibody with the best potency, CAP256V2LS-J3-3, neutralizes 98% of the 208-strain panel with a geometric mean IC80 of 0.036 mg / ml (Zhang et al., MAbs 15:2165390, 2023), and tri- specific antibody N6-PGDM1400-10E8v4 neutralizes 99% with a geometric mean IC80 of 0.073 mg / ml (Xu et al., Science 358:85-90, 2017). If VRC01 had comparable potency, the prevention efficacy would be expected to exceed 90% in the antibody mediated prevention (AMP) study (Corey et al., N Engl J Med 384:1003-1014, 2021; Mkhize et al., PLoS Pathog 19:e1011469, 2023; Seaton et al., EBioMedicine 93:104590, 2023).4239-111089-02Example 7 Treatment of HIV-1 using an HIV-1 Env specific bispecific antibody This example describes a particular method that can be used to treat HIV-1 infection in a human subject by administration of a disclosed HIV-1 Env-specific bispecific antibody. Although particular methods, dosages, and modes of administrations are provided, one skilled in the art will appreciate that variations can be made without substantially affecting the treatment. Based upon the teaching disclosed herein, HIV-1 infection can be treated by administering a therapeutically effective amount of one or more of the neutralizing bispecific described herein, thereby reducing or eliminating HIV-1 infection. Screening subjects In particular examples, the subject is first screened to determine if they have an HIV-1 infection. Examples of methods that can be used to screen for HIV-1 infection include a combination of measuring a subject’s CD4+ T cell count and the level of HIV-1 virus in serum blood levels. Additional methods using an HIV-1 Env-specific antibody described herein can also be used to screen for HIV-1 infection. In some examples, HIV-1 testing consists of initial screening with an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to HIV-1. Specimens with a nonreactive result from the initial ELISA are considered HIV-1-negative unless new exposure to an infected partner or partner of unknown HIV-1 status has occurred. Specimens with a reactive ELISA result are retested in duplicate. If the result of either duplicate test is reactive, the specimen is reported as repeatedly reactive and undergoes confirmatory testing with a more specific supplemental test (e.g., Western blot or an immunofluorescence assay (IFA)). Specimens that are repeatedly reactive by ELISA and positive by IFA or reactive by Western blot are considered HIV-positive and indicative of HIV-1 infection. Specimens that are repeatedly ELISA-reactive occasionally provide an indeterminate Western blot result, which may be either an incomplete antibody response to HIV-1 in an infected person, or nonspecific reactions in an uninfected person. IFA can be used to confirm infection in these ambiguous cases. In some instances, a second specimen will be collected more than a month later and retested for subjects with indeterminate Western blot results. In additional examples, nucleic acid testing (e.g., viral RNA or proviral DNA amplification method) can also help diagnosis in certain situations.4239-111089-02The detection of HIV-1 in a subject’s blood is indicative that the subject is infected with HIV-1 and is a candidate for receiving the therapeutic compositions disclosed herein. Moreover, detection of a CD4+ T cell count below 350 per microliter, such as 200 cells per microliter, is also indicative that the subject is likely to have an HIV-1 infection. Pre-screening is not required prior to administration of the therapeutic compositions disclosed herein Pre-treatment of subjects In particular examples, the subject is treated prior to administration of a therapeutic agent that includes one or more antiretroviral therapies known to those of skill in the art. However, such pre-treatment is not always required, and can be determined by a skilled clinician. Administration of therapeutic compositions Following subject selection, a therapeutically effective dose of a HIV-1 Env-specific bispecific antibody described herein is administered to the subject (such as an adult human or a newborn infant either at risk for contracting HIV-1 or known to be infected with HIV-1). Additional agents, such as anti-viral agents, can also be administered to the subject simultaneously or prior to or following administration of the disclosed agents. Administration can be achieved by any method known in the art, such as oral administration, inhalation, intravenous, intramuscular, intraperitoneal, or subcutaneous. The amount of the composition administered to prevent, reduce, inhibit, and / or treat HIV-1 or a condition associated with it depends on the subject being treated, the severity of the disorder, and the manner of administration of the therapeutic composition. Ideally, an amount of the bispecific antibody that is sufficient to prevent, reduce, and / or inhibit, and / or treat the condition (e.g., HIV-1) in a subject without causing a substantial cytotoxic effect in the subject is administered. An effective amount can be readily determined by one skilled in the art, for example using routine trials establishing dose response curves. As such, these compositions may be formulated with an inert diluent or with a pharmaceutically acceptable carrier. In one specific example, antibodies are administered at 5 mg per kg every two weeks or 10 mg per kg every two weeks. In another example, antibodies are administered at 50 µg per kg given twice a week for 2 to 3 weeks.4239-111089-02Administration of the therapeutic compositions can be taken long term (for example over a period of months or years). Assessment Following the administration of one or more therapies, subjects with HIV-1 can be monitored for reductions in HIV-1 levels, increases in a subject’s CD4+ T cell count, or reductions in one or more clinical symptoms associated with HIV-1 disease. In particular examples, subjects are analyzed one or more times, starting 7 days following treatment. Subjects can be monitored using any method known in the art. For example, biological samples from the subject, including blood, can be obtained and alterations in HIV-1 or CD4+ T cell levels evaluated. Additional treatments In particular examples, if subjects are stable or have a minor, mixed or partial response to treatment, they can be re-treated after re-evaluation with the same schedule and preparation of agents that they previously received for the desired amount of time, including the duration of a subject’s lifetime. A partial response is a reduction, such as at least a 10%, at least 20%, at least 30%, at least 40%, at least 50%, or at least 70% in HIV-1 infection, HIV-1 replication or combination thereof. A partial response may also be an increase in CD4+ T cell count such as at least 350 T cells per microliter. It will be apparent that the precise details of the methods or compositions described may be varied or modified without departing from the spirit of the described implementations. We claim all such modifications and variations that fall within the scope and spirit of the claims below.

Claims

4239-111089-02We claim:

1. A bispecific antibody, comprising: a first binding domain comprising an antibody comprising a heavy chain variable region (VH) comprising a heavy chain complementarity determining region (HCDR)1, a HCDR2, and a HCDR3 of the VHsequence set forth as SEQ ID NO: 25 (CAP256V2LS), a light chain variable region (VL), and a constant domain; a second binding domain comprising a single-domain antibody or multimer thereof of wherein the single-domain antibody comprises the complementarity determining region 1 (CDR1), CDR2 and CDR3 of one of the single-domain antibody sequences set forth as (a) SEQ ID NO: 1 (G36), (b) SEQ ID NO: 5 (G36 K64E), (c) SEQ ID NO: 7 (R27), or (d) SEQ ID NO: 11 (R27 K64E); wherein the first binding domain specifically binds to a V1-V2 region of HIV-1 Envelope protein (Env), and the second binding domain specifically binds to a CD4 binding site of HIV-1 Env; wherein the first and second binding domains can simultaneously bind to a single HIV-1 Env trimer; wherein the C-terminus of the VHH is fused to the N terminus of the VL by a peptide linker; and wherein the bispecific antibody neutralizes HIV-1.

2. The bispecific antibody of claim 1, wherein the CDR sequences are defined according to the Kabat or IMGT convention.

3. The bispecific antibody of any one of the prior claims, wherein the CDR1, CDR2, and CDR3 of the single-domain antibody comprise sequences set forth as one of: (a) SEQ ID NOs: 2, 3, and 4, respectively (G36 CDRs); (b) SEQ ID NOs: 2, 6, and 4, respectively (G36 K64E CDRs); (c) SEQ ID NOs: 8, 9, and 10, respectively (R27 CDRs); or (d) SEQ ID NOs: 8, 12, and 10, respectively (R27 K64E CDRs).

4. The bispecific antibody of any one of the prior claims, wherein the CDR1, CDR2, and CDR3 of the single-domain antibody comprise sequences set forth as one of:4239-111089-02(a) SEQ ID NOs: 2, 3, and 4, respectively, and the remaining portion of the single- domain antibody comprises an amino acid sequence at least 90% identical to SEQ ID NO: 1; (b) SEQ ID NOs: 2, 6, and 4, respectively, and the remaining portion of the single- domain antibody comprises an amino acid sequence at least 90% identical to SEQ ID NO: 5; (c) SEQ ID NOs: 8, 9, and 10, respectively, and the remaining portion of the single- domain antibody comprises an amino acid sequence at least 90% identical to SEQ ID NO: 7; or (d) SEQ ID NOs: 8, 12, and 10, respectively, and the remaining portion of the single- domain antibody comprises an amino acid sequence at least 90% identical to SEQ ID NO:

11.

5. The bispecific antibody of any one of the prior claims, wherein the single- domain antibody comprises one or more amino acid substitutions in the framework regions to replace positively charged amino acids with neutral or negatively charged amino acids.

6. The bispecific antibody of claim 5, wherein the single-domain antibody comprises a R19E substitution in the framework region (FR) 1, or a K43E substitution in the FR2, or both the R19E and K43E substitutions (Kabat numbering).

7. The bispecific antibody of any one of the prior claims, wherein the amino acid sequence of the single-domain antibody comprises or consists of: SEQ ID NO: 1 (G36); SEQ ID NO: 13 (G36 R19E); SEQ ID NO: 5 (G36 K64E); SEQ ID NO: 14 (G36 R19E, K43E, K64E); SEQ ID NO: 7 (R27); SEQ ID NO: 15 (R27 R19E); SEQ ID NO: 11 (R27 K64E); or SEQ ID NO: 16 (R27 R19E, K43E, K64E).

8. The bispecific antibody of any one of the prior claims, wherein the antibody is a humanized antibody.

9. The bispecific antibody of any one of the prior claims, comprising the multimer of the single-domain antibody.4239-111089-0210. The bispecific antibody of claim 9, wherein the multimer is a trimer.

11. The bispecific antibody of claim 10, wherein the trimer of the single-domain antibody comprises an amino acid sequence set forth as any one of: SEQ ID NO: 17 (G36x3); SEQ ID NO: 18 (G36x3 R19E); SEQ ID NO: 19 (G36x3 K64E); SEQ ID NO: 20 (G36x3 R19E, K43E, K64E); SEQ ID NO: 21 (R27x3); SEQ ID NO: 22 (R27x3 R19E); SEQ ID NO: 23 (R27x3 K64E); or SEQ ID NO: 24 (R27x3 R19E, K43E, K64E).

12. The bispecific antibody of any one of the prior claims, wherein the HCDR1, HCDR2, and HCDR3 of the VH of the first binding domain comprise amino acid sequences set forth as SEQ ID NOs: 26, 27, and 28, respectively (CAP256V2LS HCDRs).

13. The bispecific antibody of any one of the prior claims, wherein the VH comprises the HCDR1, HCDR2, and HCDR3 set forth as SEQ ID NOs: 26, 27, and 28, respectively, and the remainder of the VH is at least 90% identical to SEQ ID NO:

25.

14. The bispecific antibody of any one of the prior claims, wherein the VL comprises a light chain complementarity determining region (LCDR)1, a LCDR2, and a LCDR3 comprising amino acid sequences set forth as SEQ ID NOs: 30, 31, and 32, respectively (CAP256V2LS LCDRs).

15. The bispecific antibody of any one of the prior claims, wherein the LCDR1, LCDR2, and LCDR3 of the VLcomprise amino acid sequences set forth as SEQ ID NOs: 30, 31, and 32, respectively (CAP256V2LS LCDRs) and the remainder of the VL is at least 90% identical to SEQ ID NO:

29.

16. The bispecific antibody of any one of the prior claims, wherein the VHcomprises or consists of the amino acid sequence set forth as SEQ ID NO: 25.4239-111089-0217. The bispecific antibody of any one of the prior claims, wherein the VLcomprises or consists of the amino acid sequence set forth as SEQ ID NO:

29.

18. The bispecific antibody of any one of the prior claims, wherein: the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 1 (G36); the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 13 (G36 R19E); the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 5 (G36 K64E); the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 14 (G36 R19E, K43E, K64E); the antibody of the first binding domain comprises a VHand a VLcomprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 7 (R27); the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 15 (R27 R19E); the antibody of the first binding domain comprises a VHand a VLcomprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof4239-111089-02comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 11 (R27 K64E); or the antibody of the first binding domain comprises a VH and a VL comprising or consisting of the amino acid sequences set forth as SEQ ID NO: 25 and 29, respectively, and the second binding domain comprises a single-domain antibody or multimer thereof comprising or consisting of the amino acid sequence set forth as SEQ ID NO: 16 (R27 R19E, K43E, K64E).

19. The bispecific antibody of any one of the prior claims, wherein the peptide linker is from 5-30 amino acids in length.

20. The bispecific antibody of claim 19, wherein the peptide linker is from 10-20 amino acids in length.

21. The bispecific antibody of claim 19, wherein the peptide linker is 15 amino acids in length.

22. The bispecific antibody of any one of the prior claims, wherein the peptide linker is a glycine-serine linker.

23. The bispecific antibody of any one of the prior claims, wherein the peptide linker comprises or consists of the amino acid sequence set forth as SEQ ID NO:

43.

24. The bispecific antibody of claim 1, wherein the VH comprises the amino acid sequences set forth as SEQ ID NO: 25, and the single-domain antibody fused to the VLcomprises an amino acid sequence set forth as: amino acids 1-251 of SEQ ID NO: 33 or 34; amino acids 1-531 of SEQ ID NO: 35, 36, or 37; amino acids 1-247 of SEQ ID NO: 38 or 39; or amino acids 1-519 of SEQ ID NO: 40, 41, or 42.

25. The bispecific antibody of any one of the prior claims, wherein the antibody is a recombinant IgG, IgM or IgA.4239-111089-0226. The bispecific antibody of any one of the prior claims, wherein the constant domain comprises a modification that increases binding to the neonatal Fc receptor.

27. The bispecific antibody of claim 26, wherein the constant domain is an IgG1 constant domain comprising M428L and N434S mutations (EU numbering system).

28. The bispecific antibody of claim 22, wherein the heavy chain of the antibody comprises the amino acid sequence set forth as SEQ ID NO: 30 and the VHH fused to the light chain of the antibody comprises the amino acid sequence set forth as any one of SEQ ID NOs: 33-42.

29. The bispecific antibody of any one of the prior claims, wherein the bispecific antibody neutralizes HIV-1.

30. A single-domain antibody that specifically binds human immunodeficiency virus 1 (HIV-1) Envelope (Env) protein, wherein the single-domain antibody comprises the complementarity determining region 1 (CDR1), CDR2, and CDR3 sequences of (a) SEQ ID NO: 1 (G36); (b) SEQ ID NO: 5 (G36 K64E); (c) SEQ ID NO: 7 (R27); or (d) SEQ ID NO: 11 (R27 K64E).

31. The single-domain antibody of claim 30, wherein the CDR sequences are defined according to the Kabat or IMGT convention.

32. The single-domain antibody of claim 30 or claim 31, wherein the CDR1, CDR2, and CDR3 comprise sequences set forth as one of: (a) SEQ ID NOs: 2, 3, and 4, respectively (G36 CDRs); (b) SEQ ID NOs: 2, 6, and 4, respectively (G36 K64E CDRs); (c) SEQ ID NOs: 8, 9, and 10, respectively (R27 CDRs); or (d) SEQ ID NOs: 8, 12, and 10, respectively (R27 K64E CDRs).

33. The single-domain antibody of any one of claims 30-32, wherein the CDR1, CDR2, and CDR3 comprise sequences set forth as one of:4239-111089-02(a) SEQ ID NOs: 2, 3, and 4, respectively, and the remaining portion of the single- domain antibody comprises an amino acid sequence at least 90% identical to SEQ ID NO: 1; (b) SEQ ID NOs: 2, 6, and 4, respectively, and the remaining portion of the single- domain antibody comprises an amino acid sequence at least 90% identical to SEQ ID NO: 5; (c) SEQ ID NOs: 8, 9, and 10, respectively, and the remaining portion of the single- domain antibody comprises an amino acid sequence at least 90% identical to SEQ ID NO: 7; or (d) SEQ ID NOs: 8, 12, and 10, respectively, and the remaining portion of the single- domain antibody comprises an amino acid sequence at least 90% identical to SEQ ID NO:

11.

34. The single-domain antibody of any one of claims 30-33, comprising one or more amino acid substitutions in the framework regions to replace positively charged amino acids with neutral or negatively charged amino acids.

35. The single-domain antibody of claim 34, further comprising a R19E substitution in the framework region (FR) 1, or a K43E substitution in the FR2, or both the R19E and K43E substitutions (Kabat numbering).

36. The single-domain antibody of any one of claims 30-35, wherein the amino acid sequence of the single-domain antibody comprises or consists of: SEQ ID NO: 1 (G36); SEQ ID NO: 13 (G36 R19E); SEQ ID NO: 5 (G36 K64E); SEQ ID NO: 14 (G36 R19E, K43E, K64E); SEQ ID NO: 7 (R27); SEQ ID NO: 15 (R27 R19E); SEQ ID NO: 11 (R27 K64E); or SEQ ID NO: 16 (R27 R19E, K43E, K64E).

37. The single-domain antibody of any one of claims 30-36, wherein the antibody is a humanized antibody.

38. The single-domain antibody of any one of claims 30-37, wherein the antibody neutralizes HIV-1.4239-111089-0239. A multimer of the single-domain antibody of any one of claims 30-38.

40. The multimer of claim 39, comprising a trimer of the single-domain antibody.

41. The multimer of claim 40, wherein the trimer comprises an amino acid sequence set forth as any one of SEQ ID NO: 17 (G36x3); SEQ ID NO: 18 (G36x3 R19E); SEQ ID NO: 19 (G36x3 K64E); SEQ ID NO: 20 (G36x3 R19E, K43E, K64E); SEQ ID NO: 21 (R27x3); SEQ ID NO: 22 (R27x3 R19E); SEQ ID NO: 23 (R27x3 K64E); or SEQ ID NO: 24 (R27x3 R19E, K43E, K64E).

42. The single-domain antibody or multimer thereof of any one of claims 30-41, fused to a heterologous protein.

43. The single-domain antibody or multimer of claim 42, wherein the heterologous protein comprises a human Fc protein.

44. The single-domain antibody or multimer of claim 43, wherein the human Fc protein comprises a modification that increases half-life of the fusion protein.

45. The single-domain antibody or multimer of claim 44, wherein the modification increases binding to the neonatal Fc receptor.

46. The single-domain antibody or multimer of claim 43, wherein the human Fc protein is an IgG2a Fc comprising the amino acid sequence set forth as SEQ ID NO:

51.

47. The single-domain antibody or multimer of claim 43, wherein the single- domain antibody or multimer thereof fused to the human Fc protein comprises the amino acid sequence set forth as SEQ ID NO: 52 (G36x3-IgG2a) or SEQ ID NO: 53 (R27x3-IgG2a).4239-111089-0248. A multispecific antibody comprising the single-domain antibody or fusion protein of any one of claims 30-47.

49. The bispecific antibody, single-domain antibody, multimer, or multispecific antibody of any one of the prior claims, linked to an effector molecule or a detectable marker.

50. A nucleic acid molecule encoding the bispecific antibody, single-domain antibody, multimer, or multispecific antibody of any one of the prior claims of any one of the prior claims.

51. The nucleic acid molecule of claim 50, operably linked to a promoter.

52. An expression vector comprising the nucleic acid molecule of claim 50 or claim 51.

53. A pharmaceutical composition, comprising: a therapeutically effective amount of the bispecific antibody, single-domain antibody, multimer, multispecific antibody, nucleic acid molecule, or expression vector of any one of the prior claims; and a pharmaceutically acceptable carrier.

54. A method of producing an antibody that specifically binds to HIV-1 Env, comprising: expressing the nucleic acid molecule or expression vector of any of claims 50-52 in a host cell to produce the antibody in the host cell; and purifying the antibody.

55. A method of detecting an HIV-1 infection in a subject, comprising: contacting a biological sample from the subject with the bispecific antibody, single- domain antibody, multimer, or multispecific antibody of any one of the prior claims of any of claims 1-48 under conditions sufficient to form an immune complex; and detecting the presence of the immune complex in the sample, wherein the presence of the immune complex in the sample indicates that the subject has the HIV-1 infection.4239-111089-0256. A method of inhibiting an HIV-1 infection in a subject, comprising administering to the subject an amount of the bispecific antibody, single-domain antibody, multimer, multispecific antibody, nucleic acid molecule, expression vector, or pharmaceutical composition of any of claims 1-53 effective to prevent or treat the HIV-1 infection in the subject.

57. The method of claim 56, wherein the subject is at risk of or has an HIV-1 infection.

58. The method of claim 56, wherein the subject has an HIV-1 infection and the method treats the infection in the subject.

59. The method of claim 56, wherein the subject is at risk of an HIV-1 infection and the method inhibits seroconversion to HIV-1 positive status in the subject.

60. Use of the bispecific antibody, single-domain antibody, multimer, multispecific antibody, nucleic acid molecule, expression vector, host cell, or pharmaceutical composition of any of claims 1-53 to inhibit HIV-1 infection in a subject.

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