Antigen-binding polypeptides, antigen-binding polypeptide complexes, and methods of their use in HIV

Abstract

Disclosed are antigen-binding polypeptides and antigen-binding polypeptide complexes (e.g., antibodies and antigen-binding fragments thereof) that bind to HIV proteins and have specific structural characteristics. Also disclosed are polynucleotides and vectors encoding such polypeptides and polypeptide complexes; host cells; chimeric antigen receptors (CARs); immune cells; pharmaceutical compositions and kits containing such polypeptides and polypeptide complexes; and methods of using such polypeptides and polypeptide complexes in HIV.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Application No. 63 / 249,722, filed September 29, 2021, which is incorporated herein by reference in its entirety.

[0002] REFERENCE TO ELECTRONICALLY SUBMITTED SEQUENCE LISTING The contents of the electronically submitted sequence listing (Name: 4850_006PC01_Seqlisting_ST26, Size: 196,015 bytes, Creation Date: September 26, 2022) are incorporated by reference in their entirety into this specification.

[0003] Field The present disclosure relates to antigen-binding polypeptides and antigen-binding polypeptide complexes (e.g., antibodies and antigen-binding fragments thereof) that specifically bind to HIV proteins and have certain structural characteristics. The present disclosure also relates to polynucleotides and vectors encoding such polypeptides and polypeptide complexes, host cells, chimeric antigen receptors (CARs), immune cells, pharmaceutical compositions and kits containing such polypeptides and polypeptide complexes, and methods of using such polypeptides and polypeptide complexes. [Background technology]

[0004] background Human immunodeficiency virus (HIV) is a major infectious disease burden with significant impact on healthcare and economies worldwide. Approximately 38 million people worldwide are infected with HIV, and more than 30 million people have died from acquired immune deficiency syndrome (AIDS), a chronic disease of immune weakening caused by HIV infection. “Global Health Sector Strategy On HIV-2016-2021-Towards Ending AIDS”, World Health Organization, June, 2016 (Non-Patent Document 1). There are two major forms of HIV: HIV-1 and HIV-2. HIV-1 is more prevalent worldwide, while HIV-2 is less pathogenic and is mainly restricted to West Africa.

[0005] The major structural proteins of HIV are Gag, Pol, and Env. Gag (group specific antigen) is a structural protein of the viral core. Pol is a polyprotein that contains the enzymes important for viral replication: protease (PR), reverse transcriptase (RT), and integrase (IN). Env (envelope) encodes the glycoprotein that forms the outer envelope of the virus. Env is synthesized as a precursor glycoprotein gp160, which is subsequently processed to gp120 and gp41. Env interacts with the primary receptor CD4 and co-receptors (e.g., chemokine receptor CCR5) to fuse the viral membrane with the target cell membrane.

[0006] Env genetic diversity and glycan shielding have hindered the development of innate immunity against HIV and posed challenges to conventional vaccine development, but also prompted the search for alternative approaches to HIV prevention, one of the top global health priorities.

[0007] Despite the large number of anti-HIV / AIDS drugs available, HIV patients still face the daily challenge of taking multiple drugs under strict regimens. Inevitably, most patients will suffer the consequences of the emergence of drug-resistant viral mutants and develop other health problems such as cardiovascular disease, kidney disease, diabetes, bone disease, liver disease, cognitive impairment, etc., due to the toxicity of long-term anti-HIV drugs. Alternative treatment options are urgently needed for HIV / AIDS patients.

[0008] Broadly neutralizing HIV-1 antibodies (bnAbs) are antibodies that neutralize multiple HIV-1 virus strains. The fact that bnAbs target conserved epitopes in the virus means that the targeted epitopes are likely to remain even if the virus mutates. Therefore, bnAbs have recently been considered for the treatment and prevention of HIV / AIDS. Human clinical trials have revealed two factors that are important for the efficacy of bnAbs. First, the minimal effective dose or trough level of circulating bnAbs must be exceeded to prevent infection. Second, the emergence of viral escape through resistance mutations must be prevented.

[0009] Early human clinical trials using bnAbs demonstrated the feasibility and safety of this approach with transient reductions in viral load and acceptable tolerability and immunogenicity. Burton et al., Annu. Rev. Immunol. 34: 635-659 (2016); Mascola et al., Immunol. Rev. 254: 225-244 (2013); Wu et al., Science. 329: 856-861 (2010). However, resistant HIV strains emerged rapidly after treatment with individual bnAbs in vitro and in vivo. More recently, a phase II clinical trial using VRC01 bnAb highlighted the importance of maintaining adequate circulating antibody levels to reduce acquisition rates and suggested that effective prevention requires antibody combination therapy to enhance efficacy and minimize escape mutations. Corey et al., N. Engl. J. Med. 384:1003-1014 (2021) (Non-patent Document 5).

[0010] Multispecific antibodies address the limitations of bnAbs by providing a single antibody type that recognizes multiple independent binding sites on the HIV-1 envelope protein. Xu et al., Science.358(6359):85-90(2017) (Non-Patent Document 6). Treatment with multispecific antibodies also ensures that the independent binding specificities are maintained with the same pharmacokinetics, while treatment with multiple single-targeting antibodies results in different antibody half-lives that decline at different rates. Furthermore, multispecific antibodies simplify the manufacturing and regulatory process by using one product for clinical development rather than combining multiple products.

[0011] Multispecific anti-HIV antibodies therefore provide an important technological platform for the development of neutralizing antibody-based therapies to treat HIV / AIDS, offering a drug class with lower long-term toxicity and significantly less frequent treatment regimens. Multispecific antibodies also complement existing drugs by using completely different HIV targets than current standard of care HIV / AIDS drugs, providing patients with an alternative for disease control and health management. Multispecific antibodies may also provide a meaningful approach to HIV prevention in the current absence of an effective HIV vaccine.

[0012] In addition, the development of therapeutic antibodies can be challenging, especially in the manufacturing and later stages of development. For example, the manufacture of multispecific antibodies often requires multiple genes or plasmids for cell line development, which must be delivered to the same cell to make the correct molecule. Furthermore, multispecific antibodies can have mispairing between heavy and light chains, which can reduce product yields, increase the burden of cell line colony screening efforts, and cause product heterogeneity.

[0013] Thus, there is a need for multispecific and multifunctional antibodies, antigen-binding polypeptides, and antigen-binding polypeptide complexes that can bind to HIV proteins for selectivity or breadth / neutralization, can bring together two or more cell types, can bring targets together to transmit activation signals, can modify the HIV microenvironment, and can enhance avidity to improve efficacy. [Prior art documents] [Non-patent literature]

[0014] [Non-Patent Document 1] “Global Health Sector Strategy On HIV-2016-2021-Towards Ending AIDS”,World Health Organization,June,2016 [Non-Patent Document 2] Burton et al.,Annu.Rev.Immunol.34:635-659(2016) [Non-Patent Document 3] Mascola et al.,Immunol.Rev.254:225-244(2013) [Non-Patent Document 4] Wu et al.,Science.329:856-861(2010) [Non-Patent Document 5] Corey et al.,N.Engl.J.Med.384:1003-1014(2021) [Non-Patent Document 6] Xu et al.,Science.358(6359):85-90(2017) [Brief description of the drawings]

[0015] Some aspects of the invention are herein described, by way of example only, with reference to the accompanying drawings, in which: Reference will now be made specifically to the drawings in detail, it being stressed that particulars shown are by way of example and are intended to illustrate aspects of the invention. [Figure 1] 1 shows non-limiting examples of different configurations of tetraspecific antibody molecules. [Figure 2A] A non-limiting example of a trispecific antibody construct called MX894 (VRC01scFv / PGT121x10e8v4L1IgG1LS) is shown. [Figure 2B] MX894 was analyzed by biolayer interferometry (BLI) for binding to the 10e8 fusion peptide. [Figure 2C] MX894 was analyzed by biolayer interferometry (BLI) for CD4 site-dependent binding to the HIV spike protein. [Figure 2D] MX894 was analyzed by biolayer interferometry (BLI) for CD4 site-independent binding to the HIV spike protein. [Figure 3A]A further non-limiting example of a tetraspecific antibody construct called MX873 (VRC26.25×10-1074L9 / VRC01×PGT121L1 IgG1LS) is shown. [Figure 3B] MX873 was analyzed by biolayer interferometry (BLI) for CD4 site-dependent binding to the HIV spike protein. [Figure 3C] MX873 was analyzed by biolayer interferometry (BLI) for CD4 site-independent binding to the HIV spike protein. [Figure 4A] A further non-limiting example of a tetraspecific antibody construct called MX875 (10-1074 x VRC26.25L9 / VRC01 x PGT121L1 IgG1LS) is shown. [Figure 4B] MX875 was analyzed by biolayer interferometry (BLI) for CD4 site-dependent binding to the HIV spike protein. [Figure 4C] MX875 was analyzed by biolayer interferometry (BLI) for CD4 site-independent binding to the HIV spike protein. [Figure 5A] A further non-limiting example of a tetraspecific antibody construct called MX877 (STAR_VRC26.25 x PGT128L9 / STAR_VRC01 x PGT121L1 IgG1LS) is shown. [Figure 5B] MX877 was analyzed by biolayer interferometry (BLI) for CD4 site-dependent binding to the HIV spike protein. [Figure 5C] MX877 was analyzed by biolayer interferometry (BLI) for CD4 site-independent binding to the HIV spike protein. Summary of the Invention

[0016] overview Provided herein are antigen-binding polypeptides having a structure represented by VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; or VH1-L1-VH2-L2-VL2-L3-VL1, where VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, and L3 are amino acid linkers.

[0017] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide has a structure represented by VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; or VH1-L1-VH2-L2-VL2-L3-VL1; the second polypeptide has a structure represented by VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; or or VH1-L1-VH2-L2-VL2-L3-VL1; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, and L3 are amino acid linkers.

[0018] Provided herein are antigen-binding polypeptides having a structure represented by VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; wherein VL1 is a first immunoglobulin that specifically binds to an HIV protein. VL1 is a light chain variable region; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, and L4 are amino acid linkers.

[0019] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; VL1-L1-VH2-L2-VH2-L3-VL1-Fc; VL1-L1-VL2-L2 -VH2-L3-VH1-L4-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; the second polypeptide is Fc; VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-F c; VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising an immunoglobulin heavy chain constant region 2 (CH2), an immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, and L4 are amino acid linkers.

[0020] Provided herein are VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL; VL1-L1-VL2-L2-VH2-L3-VL1-L4-CH1-L5-CL; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1. VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, and L5 are amino acid linkers.

[0021] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-CH1; VH1-VH2-VL2-VL1-CH1; VL1-VL2-VH2-VH1-CL; VH1-VH2-VL2-VL1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1; VL1-L1-VH2 L2-L2-VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1- L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1 -L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1; or VH1-L1- VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1; the second polypeptide has a structure represented by VL1-VL2-VH2-VH1-CH1; VL1-VL2-VH2-VH1-CH1; VH1-VH2-VL2-VL1-CH1; VL1-VL2-VH2-VH1-CL; VH1-VH2-VL2-VL1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CH1-CL; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1 1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L 4-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1 -L4-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1;or has a structure represented by VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, and L5 are amino acid linkers;

[0022] Provided herein are VL1-VL2-VH2-VH1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-CH1-Fc; VH1-VH2-VL2-VL1-CL-CH1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-Fc;VL1-L1-VL2-L2-VH2 -L3-VH1-L4-CH1-L5-CL-L6-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L6-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-C and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0023] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-CH1-Fc; VH1-VH2-VL2-VL1-CH1-Fc; VL1-VL2-VH2-VH1-CL-Fc; VH1-VH2-VL2-VL1-CL-Fc; VL1-VL2-VH2-VH1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-CH1-Fc; VH1-VH2-VL2-VL 1-CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;VH1-L1-VH2-L2- VL2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1- VH2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5 -CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL1-L1-VL2-L2- VH2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5- CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL 2-L3-VL1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc;VH 1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4 -CH1-L5-CL-L6-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L6-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc; the second polypeptide has a structure represented by Fc; VL1-VL2-VH2-VH1-CH1-Fc; VH1-VH2-VL2-VL1-CH1-Fc; VL1-VL2-VH2-VH1-CL-Fc;VH1-VH2-VL2-VL1-CL-Fc;VL1-VL2-VH2-VH1-CH1-CL-Fc;VH1-VH2-VL2-VL1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CL-CH1-Fc;VH1-VH2-VL2-VL1-CL-CH1 -Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-V L1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1-VH2-L2- VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL1-L1-VL2-L2-VH2-L3 -VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-Fc ;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL2-L3-V L1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc;VH1-L1-V H2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1- VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L6-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; 3-VL1-L4-CL-L5-CH1-L6-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is an immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region;Fc is a region containing immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, and L6 are amino acid linkers;

[0024] What is provided in this specification is an antigen-binding polypeptide complex containing the 1st polypeptide and the 2nd polypeptide; the 1st polypeptide is VL1-VL2-VH2-VH1; 1-L1-VH2-L2-VL2-L3-VL1;VL1-VL2-VH2-VH1-Fc;VH1-VH2-VL2-VL1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-Fc;VL1-L 1-VL2-L2-VH2-L3-VH1-L4-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc;VL1-VL2-VH2-VH1-CH1;VH1-VH2-VL2-VL1-CH1;VL1-VL2-VH2-VH1-CL;VH1-VH 2-VL2-VL1-CL;VL1-VL2-VH2-VH1-CH1-CL;VH1-VH2-VL2-VL1-CH1-CL;VL1-VL2-VH2-VH1-CL-CH1;VH1-VH2-VL2-VL1-CL-CH1;VL1-L1-VL2-L2-VH2- L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1-L1-VL2-L2- VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1;VH1-L1-VH2-L2-VL2-L3-V L1-L4-CL-L5-CH1;VL1-VL2-VH2-VH1-CH1-Fc;VH1-VH2-VL2-VL1-CH1-Fc;VL1-VL2-VH2-VH1-CL-Fc;VH1-VH2-VL2-VL1-CL-Fc;VL1-VL2-VH2-VH1- CH1-CL-Fc;VH1-VH2-VL2-VL1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CL-CH1-Fc;VH1-VH2-VL2-VL1-CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;<h2 style=";text-align:left;direction:ltr">VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL1-L1-VL2-L2-VH2-L3 -VL1-L4-CL-L5-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1 -L5-CL-L6-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc;またはV H1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-FcプチドはFc;VL1-VL2-VH2-VH1;VH1-VH2-VL2-VL1;VL1-L1-VL2-L2-VH2-L3-V H1;VH1-L1-VH2-L2-VL2-L3-VL1;VL1-VL2-VH2-VH1-Fc;VH1-VH2-VL2-VL1 -Fc;VL1-L1-VL2-L2-VH2-L3-VH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc;VL1-VL2-VH2-VH1-CH1;VH1-VH2-VL2-VL1-CH1;VL1-VL2-VH2-VH1-CL;VH1-VH2-VL2-VL1-CL;VL1-VL2-VH2-VH1-CH1-CL;VH1-VH2-VL2-VL1-CH1-CL;<h2 style=";text-align:left;direction:ltr">VL1-VL2-VH2-VH1-CL-CH1;VH1-VH2-VL2-VL1-CL-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1- L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1;VL1-VL2-VH2-VH1-CH1-Fc;VH1-VH2-VL2-VL1-CH1-Fc;VL1-VL2-VH2-VH1-CL-Fc;VH1-VH2-VL2-VL1-CL-Fc;VL1-VL2-VH2-VH1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CL-Fc CH1-Fc;VH1-VH2-VL2-VL1-CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH 1-L5-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VL1-L4-CL-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L6-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein. VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0025] Provided herein are VL1-VL2-VH2-VH1-Fc-Fc; VH1-VH2-VL2-VL1-Fc-Fc; VL1-L1-VL2-L2-VH 2-L3-VH1-Fc-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-Fc-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L 4-Fc-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc-L5-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc-L5-Fc. is a polypeptide or antigen-binding polypeptide complex; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, and L5 are amino acid linkers.

[0026] Provided herein are VL1-VL2-VH2-VH1-CH3; VH1-VH2-VL2-VL1-CH3; VL1-L1-VL2-L2-VH2-L3-VH1-CH3; VH1-L1-VH2-L2-VL2-L3-VL1-CH3; VL1-L1-VL2-L2-VH2-L3-VL1-CH3; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH3; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH3; VL1 -VL2-VH2-VH1-CH3-CH3;VH1-VH2-VL2-VL1-CH3-CH3;VL1-L1-VL2-L2-VH2-L3-VH1-CH3-CH3;VH1-L1-VH2- L2-VL2-L3-VL1-CH3-CH3;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH3-CH3;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH3 -CH3; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH3-L5-CH3; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH3-L5-CH3; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH3 is immunoglobulin heavy chain constant region 3; and L1, L2, L3, L4, and L5 are amino acid linkers.

[0027] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide has a structure represented by VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; or VH1-L1-VH2-L2-VL2-L3-VL1; the second polypeptide has a structure represented by VL3-VL4-VH4-VH3; VH3-VH4-VL4-VL3; VL3-L4-VL4-L5-VH4-L6-VH3; or VH3-L4-VH4-L5-VL4-L6-VL3; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL2 is a H VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0028] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; or VH1-L1-VH2-L2-VL2-L3-VH1-L4-Fc. VL1-L4-Fc; the second polypeptide has a structure represented by VL3-VL4-VH4-VH3-Fc; VH3-VH4-VL4-VL3-Fc; VL3-L5-VL4-L6-VH4-L7-VH3-Fc; VH3-L5-VH4-L6-VL4-L7-VL3-Fc; VL3-L5-VL4-L6-VH4-L7-VH3-L8-Fc; or VH3-L5-VH4-L6-VL4-L7-VL3-L8-Fc; and VL1 is an HIV protein. VH1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, L6, L7, and L8 are amino acid linkers.

[0029] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide, the first polypeptide being VL1-VL2-VH2-VH1-CH1; VH1-VH2-VL2-VL1-CH1; VL1-VL2-VH2-VH1-CL; VH1-VH2-VL2-VL1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1; VL1- L1-VL2-L2-VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4- CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1; has a structure represented by VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1; the second polypeptide has a structure represented by VL3-VL4-VH4-VH3-CH1; VH3-VH4-VL4-VL3-CH1; VL3-VL4-VH4-VH3-CL; VH3-VH4-VL4-VL3-CL; VL3-VL4-VH4-VH3-CH1-CL; VH3-VH4-VL4-VL3-CH1-CL; VL3-VL4-VH4-VH3-CL-CH1; VH3-VH4-VL4-VL3-CL-CH1; VL3-VL4-VH4-VH3-CL-CH1; VH3-VH4-VL4-VL3-CL-CH1; VL3-L 6-VL4-L7-VH4-L8-VH3-L9-CH1;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CH1; VL3-L6-VL4-L7-VH4-L8-VH3-L9-CL;VH3-L6-VH4-L7-VL4-L8-VL3-L9-C L;VL3-L6-VL4-L7-VH4-L8-VH3-L9-CH1-L10-CL;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CH1-L10-CL;VL3-L6-VL4-L7-VH4-L8-VH3-L9-CL-L10-CH1;or having a structure represented by VH3-L6-VH4-L7-VL4-L8-VL3-L9-CL-L10-CH1; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; and VH1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, and L10 are amino acid linkers.

[0030] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-CH1-Fc; VH1-VH2-VL2-VL1-CH1-Fc; VL1-VL2-VH2-VH1-CL-Fc; VH1-VH2-VL2-VL1-CL-Fc; VL1-VL2-VH2-VH1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-CH1-Fc; VH1-VH2-VL2-VL 1-CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;VH1-L1-VH2-L2- VL2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1 -VH2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L 5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL1-L1-VL2-L2 -VH2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5 -CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-V L2-L3-VL1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc;V H1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L 4-CH1-L5-CL-L6-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L6-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc; and the second polypeptide has a structure represented by VL3-VL4-VH4-VH3-CH1-Fc; VH3-VH4-VL4-VL3-CH1-Fc; VL3-VL4-VH4-VH3-CL-Fc;VH3-VH4-VL4-VL3-CL-Fc;VL3-VL4-VH4-VH3-CH1-CL-Fc;VH3-VH4-VL4-VL3-CH1-CL-Fc;VL3-VL4-VH4-VH3-CL-CH1-Fc;VH3-VH4-VL4-VL3-CL-C H1-Fc;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CH1-Fc;VH3-L7-VH4-L8-VL4- L9-VL3-L10-CH1-Fc;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CL-Fc;VH3-L7-V VL3-L7-VH4-L8-VL4-L9-VL3-L10-CH1-L11-CL-Fc;VL3-L7-V L4-L8-VH4-L9-VH3-L10-CL-L11-CH1-Fc;VH3-L7-VH4-L8-VL4-L9-VL3-L10-CL-L11-CH1-Fc;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CH1-L11-Fc;VH3 -L7-VH4-L8-VL4-L9-VL3-L10-CH1-L11-Fc;VL3-L7-VL4-L8-VH4-L9-VH 3-L10-CL-L11-Fc;VH3-L7-VH4-L8-VL4-L9-VL3-L10-CL-L11-Fc;VL3-L 7-VL4-L8-VH4-L9-VH3-L10-CH1-L11-CL-L12-Fc;VH3-L7-VH4-L8-VL4- L9-VL3-L10-CH1-L11-CL-L12-Fc;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CL- or VH3-L7-VH4-L8-VL4-L9-VL3-L10-CL-L11-CH1-L12-Fc; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein;VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region that includes immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, and L12 are amino acid linkers;

[0031] What is provided in this specification is an antigen-binding polypeptide complex containing the 1st polypeptide and the 2nd polypeptide; the 1st polypeptide is VL1-VL2-VH2-VH1; VL2-VL1-Fc;VL1-VL2-VH2-VH1-CH1;VH1-VH2-VL2-VL1-CH1;VL1-VL2-VH2-VH1-CL;VH1-VH2-VL2-VL1-CL;VL1-VL2-VH2-VH1-CH1-CL;VH1-VH2-VL 2-VL1-CH1-CL;VL1-VL2-VH2-VH1-CL-CH1;VH1-VH2-VL2-VL1-CL-CH1;VL1-VL2-VH2-VH1-CH1-Fc;VH1-VH2-VL2-VL1-CH1-Fc;VL1-VL2-VH2-VH1-C L-Fc;VH1-VH2-VL2-VL1-CL-Fc;VL1-VL2-VH2-VH1-CH1-CL-Fc;VH1-VH2-VL2-VL1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CL-CH1-Fc;VH1-VH2-VL2-VL1-CL -CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1;VH1-L1-VH2-L2-VL2-L3-VL1;VL1-L1-VL2-L2-VH2-L3-VH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-Fc;VL1-L1-V L2-L2-VH2-L3-VH1-L4-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1- L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L 4-CH1-L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;<h2 style=";text-align:left;direction:ltr">VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VL1-L4-CH1-L5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VH1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1 -L4-CL-L5-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L 6-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc;またはVH1-L1-VH2 -L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc 4-VH4-VH3;VH3-VH4-VL4-VL3;VL3-VL4-VH4-VH3-Fc;VH3-VH4-VL4-VL3-F c;VL3-VL4-VH4-VH3-CH1;VH3-VH4-VL4-VL3-CH1;VL3-VL4-VH4-VH3-CL;VH 3-VH4-VL4-VL3-CL;VL3-VL4-VH4-VH3-CH1-CL;VH3-VH4-VL4-VL3-CH1-CL ;VL3-VL4-VH4-VH3-CL-CH1;VH3-VH4-VL4-VL3-CL-CH1;VL3-VL4-VH4-VH3- CH1-Fc;VH3-VH4-VL4-VL3-CH1-Fc;VL3-VL4-VH4-VH3-CL-Fc;VH3-VH4-VL4 -VL3-CL-Fc;VL3-VL4-VH4-VH3-CH1-CL-Fc;VH3-VH4-VL4-VL3-CH1-CL-Fc;<h2 style=";text-align:left;direction:ltr">VL3-VL4-VH4-VH3-CL-CH1-Fc;VH3-VH4-VL4-VL3-CL-CH1-Fc;VL3-L7-VL4-L8-VH4-L9-VH3;VH3-L7-VH4-L8-VL4-L9-VL3;VL3-L7-VL4-L8-VH4-L9-VH3-Fc;VH3-L7-VH4-L8-VL4-L9-VL3-Fc;VL3-L7-VL4-L8-VH4-L9-VL3-Fc;VL3-L7-VL4-L8-VH4-L9-VH3-L10-Fc;VH3-L7-VH4-L8-VL4-L9-VL3-L10-Fc;VL3-L7-VL4-L8-VH4-L9-VH3 -L10-CH1;VH3-L7-VH4-L8-VL4-L9-VL3-L10-CH1;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CL;VH3-L7-VH4-L8-VL4-L9-VL3-L10-CL;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CH1-L11-CL;VH3-L7-VH4-L8-VL4-L9-VL3-L10-CH1-L11-CL;VH3-L7-VH4-L8-VL4-L9-VL3-L10-CH1-L11-CL;VL3-L7-VL4-L8-VH4-L9-VL3-L10-CH1-L11-CL;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CL-L11-CH1;VH3-L7-VH4-L8-VL4-L9 -VL3-L10-CL-L11-CH1;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CH1-Fc;VH3-L7-VH4-L8-VL4-L9-VL3-L10-CH1-Fc;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CL-Fc;VH3-L7-VH4-L8-VL4-L9-VL3-L10-CL-Fc;VL3-L7-VL4-L8-VH4-L9-VL3-L10-CL-Fc;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CH1-L11-CL-Fc;VH3-L7-VL4-L8-VH4-L9-VH3-L10-CH1-L11-CL-Fc;VH3-L7-VH4-L8-VL4-L9-VL3-L10-CH1-L11-CL-Fc c;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CL-L11-CH1-Fc;VH3-L7-VH4-L8-VL4-L9-VL3-L10-CL-L11-CH1-Fc;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CH1-L11-Fc;VH3-L7-VH4-L8-VL4-L9-VL3-L10-CH1-L11-Fc;VL3-L7-VL4-L8-VL4-L9-VL3-L10-CH1-L11-Fc;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CL-L11-Fc;VH3-L7-VH4-L8-VL4-L9-VL3-L10-CL-L11-Fc;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CH1-L11-CL-L12-Fc;VH3-L7-VH4-L8-VL4-L9-VL3-L10-CH1-L11-CL- L12-Fc;VL3-L7-VL4-L8-VH4-L9-VH3-L10-CL-L11-CH1-L12-Fc; or VH3-L7-VH4-L8-VL4-L9-VL3-L10-C L-L11-CH1-L12-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein. VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, and L12 are amino acid linkers.

[0032] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide has a structure represented by VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; or VH1-L1-VH2-L2-VL2-L3-VL1; the second polypeptide has a structure represented by VL3-VH3; VH3-VL3; VL3-L4-VH3; or VH3-L4-VL3; and VL1 is a first polypeptide that specifically binds to an HIV protein. VL1 is an immunoglobulin light chain variable region; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, L3, and L4 are amino acid linkers.

[0033] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; VL1-L1-VL2-L2-VH or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; the second polypeptide has a structure represented by VL3-VH3-Fc; VH3-VL3-Fc; VL3-L5-VH3-Fc; VH3-L5-VL3-Fc; VL3-L5-VH3-L6-Fc; or VH3-L5-VL3-L6-Fc; VH1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0034] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-CH1; VH1-VH2-VL2-VL1-CH1; VL1-VL2-VH2-VH1-CL; VH1-VH2-VL2-VL1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1; VL1-L1-VL2-L2-VH2 -L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1-L1-VL2-L2-V H2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1-L1-VL2-L2-VH 2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL;VL 1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1; or VH1-L1-VH2-L2-VL2-L3-VL1 -L4-CL-L5-CH1; the second polypeptide has a structure represented by VL3-VH3-CH1; VH3-VL3-CH1; VL3-VH3-CL; VH3-VL3-CL; VL3-VH3-CH1-CL; VH3-VL3-CH1-CL; VL3-VH3-CL-CH1; VH3-VL3-CL-CH1; VL3-CL-VH3-CH1; VL3-CH1-VH3-CL; VH3-CH1-VL3-CL; VH3-CL-VL3-CH1; VL3-L6-VH3-L7-CH1; VH3-L6-VL3-L7-CH1; VL3-L6-VH3- L7-CL;VH3-L6-VL3-L7-CL;VL3-L6-VH3-L7-CH1-L8-CL;VH3-L6-VL3-L7-CH1-L8-CL;VL3-L6-VH3-L7-CL-L8-CH1;VH3-L6-VL3-L7-CL-L8-CH1;VL3-L6 -CL-L7-VH3-L8-CH1;VL3-L6-CH1-L7-VH3-L8-CL;VH3-L6-CH1-L7-VL3-L8-CL;VH3-L6-CL-L7-VL3-L8-CH1;VL3-VH3-L6-CH1-CL;VH3-VL3-L6-CH1-CL;VL3-VH3-L6-CL-CH1; VH3-VL3-L6-CL-CH1; VL3-CL-L6-VH3-CH1; VL3-CH1-L6-VH3-CL; VH3-CH1-L6-VL3-CL; or VH3-CL-L6-VL3-CH1; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL3 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein. VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, and L8 are amino acid linkers.

[0035] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-CH1-Fc; VH1-VH2-VL2-VL1-CH1-Fc; VL1-VL2-VH2-VH1-CL-Fc; VH1-VH2-VL2-VL1-CL-Fc; VL1-VL2-VH2-VH1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-CH1-Fc; VH1-VH2-VL2-VL1 -CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;VH1-L1-VH2-L2-V L2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1-V H2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-C L-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL1-L1-VL2-L2-VH 2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH 1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL2-L 3-VL1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc;VH1-L1 -VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1 -L5-CL-L6-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L6-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc; the second polypeptide has a structure represented by VL3-VH3-CH1-Fc; VH3-VL3-CH1-Fc; VL3-VH3-CL-Fc; VH3-VL3-CL-Fc; VL3-VH3-CH1-CL-Fc;VH3-VL3-CH1-CL-Fc;VL3-VH3-CL-CH1-Fc;VH3-VL3-CL-CH1-Fc;VL3-CL-VH3-CH1-Fc;VL3-CH1-VH3-CL-Fc;VH3-CH1-VL3-CL-Fc;VH3-CL-VL3-CH1 -Fc;VL3-L7-VH3-L8-CH1-Fc;VH3-L7-VL3-L8-CH1-Fc;VL3-L7-VH3-L8-CL-Fc;VH3-L7-VL3-L8-CL-Fc;VL3-L7-VH3-L8-CH1-L9-CL-Fc;VH3-L7-VL 3-L8-CH1-L9-CL-Fc;VL3-L7-VH3-L8-CL-L9-CH1-Fc;VH3-L7-VL3-L8-CL-L9-CH1-Fc;VL3-L7-CL-L8-VH3-L9-CH1-Fc;VL3-L7-CH1-L8-VH3-L9-CL -Fc;VH3-L7-CH1-L8-VL3-L9-CL-Fc;VH3-L7-CL-L8-VL3-L9-CH1-Fc;VL3-L7-VH3-L8-CH1-L9-CL-L10-Fc;VH3-L7-VL3-L8-CH1-L9-CL-L10-Fc;VL3 -L7-VH3-L8-CL-L9-CH1-L10-Fc;VH3-L7-VL3-L8-CL-L9-CH1-L10-Fc;VL3-L7-CL-L8-VH3-L9-CH1-L10-Fc;VL3-L7-CH1-L8-VH3-L9-CL-L10-Fc;V H3-L7-CH1-L8-VL3-L9-CL-L10-Fc;VH3-L7-CL-L8-VL3-L9-CH1-L10-Fc;VL3-VH3-L7-CH1-CL-Fc;VH3-VL3-L7-CH1-CL-Fc;VL3-VH3-L7-CL-CH1-Fc ;VH3-VL3-L7-CL-CH1-Fc;VL3-CL-L7-VH3-CH1-Fc;VL3-CH1-L7-VH3-CL-Fc;VH3-CH1-L7-VL3-CL-Fc;orVH3-CL-L7-VL3-CH1-Fc;wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein;VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein;and VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein;VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region that includes immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, and L10 are amino acid linkers;

[0036] What is provided in this specification is an antigen-binding polypeptide complex containing the polypeptide 1 and the polypeptide 2; the polypeptide 1 is VL1-VL2-VH2-VH1; 1-L1-VH2-L2-VL2-L3-VL1;VL1-VL2-VH2-VH1-Fc;VH1-VH2-VL2-VL1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-Fc;VL1-L 1-VL2-L2-VH2-L3-VH1-L4-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc;VL1-VL2-VH2-VH1-CH1;VH1-VH2-VL2-VL1-CH1;VL1-VL2-VH2-VH1-CL;VH1-VH 2-VL2-VL1-CL;VL1-VL2-VH2-VH1-CH1-CL;VH1-VH2-VL2-VL1-CH1-CL;VL1-VL2-VH2-VH1-CL-CH1;VH1-VH2-VL2-VL1-CL-CH1;VL1-L1-VL2-L2-VH2- L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1-L1-VL2-L2- VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1;VH1-L1-VH2-L2-VL2-L3-V L1-L4-CL-L5-CH1;VL1-VL2-VH2-VH1-CH1-Fc;VH1-VH2-VL2-VL1-CH1-Fc;VL1-VL2-VH2-VH1-CL-Fc;VH1-VH2-VL2-VL1-CL-Fc;VL1-VL2-VH2-VH1- CH1-CL-Fc;VH1-VH2-VL2-VL1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CL-CH1-Fc;VH1-VH2-VL2-VL1-CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;<h2 style=";text-align:left;direction:ltr">VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3- VL1-L4-CL-L5-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5 -CL-L6-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc;またはVH1-L 1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc VL3-VH3;VH3-VL3;VL3-L4-VH3;VH3-L4-VL3;VL3-VH3-Fc;VH3-VL3-Fc;VL 3-L4-VH3-Fc;VH3-L4-VL3-Fc;VL3-VH3-CH1;VH3-VL3-CH1;VL3-VH3-CL;V H3-VL3-CL;VL3-VH3-CH1-CL;VH3-VL3-CH1-CL;VL3-VH3-CL-CH1;VH3-VL3-CL-CH1;VL3-CL-VH3-CH1;VL3-CH1-VH3-CL;VH3-CH1-VL3-CL;VH3-CL-VL3-CH1;VL3-L7-VH3-L8-CH1;VH3-L7-VL3-L8-CH1;VL3-L7-VH3-L8-CL;VH3-L7-VL3-L8-CL;VL3-L7-VH3-L8-CH1-L9-CL;VH3-L7-VL3-L8-CH1-L9-CL;<h2 style=";text-align:left;direction:ltr">VL3-L7-VH3-L8-CL-L9-CH1;VH3-L7-VL3-L8-CL-L9-CH1;VL3-L7-CL-L8-VH3-L9-CH1;VL3-L7-CH1-L8-VH3-L9-CL;VH3-L7-CH1-L8-VL3-L9-CL;VH3-L7-CL-L8-VL3-L9-CH1;VL3-VH3-L7-CH1-CL;VH3-VL3-L7-CH1-CL;VL3-VH3-L7-CL-CH1;VH3-VL3-L7-CL-CH1;VL3-CL-L7-VH3-CH1;VL3-CH1-L 7-VH3-CL;VH3-CH1-L7-VL3-CL;VH3-CL-L7-VL3-CH1;VL3-VH3-CH1-Fc;VH3-VL3-CH1-Fc;VL3-VH3-CL-Fc;VH3-VL3-CL-Fc;VL3-VH3-CH1-CL-Fc;V H3-VL3-CH1-CL-Fc;VL3-VH3-CL-CH1-Fc;VH3-VL3-CL-CH1-Fc;VL3-CL-VH3-CH1-Fc;VL3-CH1-VH3-CL-Fc;VH3-CH1-VL3-CL-Fc;VH3-CL-VL3-CH1- Fc;VL3-L7-VH3-L8-CH1-Fc;VH3-L7-VL3-L8-CH1-Fc;VL3-L7-VH3-L8-CL-Fc;VH3-L7-VL3-L8-CL-Fc;VL3-L7-VH3-L8-CH1-L9-CL-Fc;VH3-L7-VL3-L8-CH1-L9-CL-Fc;VL3-L7-VH3-L8-CL-L9-CH1-Fc;VH3-L7-VL3-L8-CL-L9-CH1-Fc;VL3-L7-VL3-L8-CL-L9-CH1-Fc;VL3-L7-VL3-L8-CL-L9-CH1-Fc;VL3-L7-CL-L8-VH3-L9-CH1-Fc;VL3-L7-CH1-L8-VH3-L9-CL- Fc;VH3-L7-CH1-L8-VL3-L9-CL-Fc;VH3-L7-CL-L8-VL3-L9-CH1-Fc;VL3-L7-VH3-L8-CH1-L9-Fc;VH3-L7-VL3-L8-CH1-L9-Fc;VL3-L7-VH3-L8-CL-L9-Fc;VH3-L7-VL3-L8-CL-L9-Fc;VL3-L7-VH3-L8-CH1-L9-CL-L10-Fc;VH3-L7-VL3-L8-CH1-L9-CL-L10-Fc;VL3-L7-VH3-L8-CL-L9-CH1-L10-Fc;VH3-L7-VL3-L8-CL-L9-CH1-L10-Fc;VL3-L7-CL-L8-VH3-L9-CH1-L10-Fc;VL3-L7-CH1-L8-VH3-L9-CL-L10-Fc ;VH3-L7-CH1-L8-VL3-L9-CL-L10-Fc;VH3-L7-CL-L8-VL3-L9-CH1-L10-Fc;VL3-VH3-L7-CH1-CL-Fc;VH3-VL3-L VH3-VH3-L7-CL-CH1-Fc; VH3-VL3-L7-CL-CH1-Fc; VL3-CL-L7-VH3-CH1-Fc; VL3-CH1-L7-VH3-CL-Fc; VH3-CH1-L7-VL3-CL-Fc; or VH3-CL-L7-VL3-CH1-Fc; wherein VL1 is a first immunoglobulin light chain that specifically binds to an HIV protein. VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, and L10 are amino acid linkers.

[0037] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide has a structure represented by VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; or VH1-L1-VH2-L2-VL2-L3-VL1; the second polypeptide has a structure represented by VL3; the third polypeptide has a structure represented by VH3; and VL1 is a first polypeptide that specifically binds to an HIV protein. VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, and L3 are amino acid linkers.

[0038] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; V or VH1-L1-VH2-L2-VL2-L3-VH1-L4-Fc; the second polypeptide has a structure represented by VL3; or VL3-L5; the third polypeptide has a structure represented by VH3-Fc; or VH3-L6-Fc; and VL1 is an HIV protein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, or L6 are amino acid linkers.

[0039] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; V L1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; the second polypeptide has a structure represented by VL3-Fc; or VL3-L5-Fc; the third polypeptide has a structure represented by VH3; or VH3-L6; and VL1 is an HIV protein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0040] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-CH1; VH1-VH2-VL2-VL1-CH1; VL1-VL2-VH2-VH1-CL; VH1-VH2-VL2-VL1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1; VL1 -L1-VL2-L2-VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL; the second polypeptide has a structure represented by VL3-CH1; VL3-CL; VL3-L6-CH1; or VL3-L6-CL; the third polypeptide has a structure represented by VH3-CH1; VH3-CL; VH3-L7-CH1; or VH3-L7-CL; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein. VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers.

[0041] What is provided in this specification is an antigen-binding polypeptide complex containing the 1st polypeptide, the 2nd polypeptide, and the 3rd polypeptide; the 1st polypeptide is VL1-VL2-VH2-VH1; L3-VH1;VH1-L1-VH2-L2-VL2-L3-VL1;VL1-VL2-VH2-VH1-Fc;VH1-VH2-VL2-VL1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-Fc c;VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc;VL1-VL2-VH2-VH1-CH1;VH1-VH2-VL2-VL1-CH1;VL1-VL2-VH2-VH1-CL; VH1-VH2-VL2-VL1-CL;VL1-VL2-VH2-VH1-CH1-CL;VH1-VH2-VL2-VL1-CH1-CL;VL1-VL2-VH2-VH1-CL-CH1;VH1-VH2-VL2-VL1-CL-CH1;VL1-L1-VL2-L2 -VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1-L1-VL2 -L2-VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1;VH1-L1-VH2-L2-VL2-L3 -VL1-L4-CL-L5-CH1;VL1-VL2-VH2-VH1-CH1-Fc;VH1-VH2-VL2-VL1-CH1-Fc;VL1-VL2-VH2-VH1-CL-Fc;VH1-VH2-VL2-VL1-CL-Fc;VL1-VL2-VH2-VH1 -CH1-CL-Fc;VH1-VH2-VL2-VL1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CL-CH1-Fc;VH1-VH2-VL2-VL1-CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3- VH1-L4-CH1-L5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-V L1-L4-CL-L5-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-C L-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-C L-L6-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc has the structure shown by; 3;VL3-Fc;VL3-CH1;VL3-CL;VL3-CH1-CL;VL3-CL-CH1;VL3-CH1-Fc;VL3-CL-Fc;VL3-CH1-CL-Fc;VL3-CL-CH1-Fc;VL3-L7-Fc;VL3-L7-CH1;VL3-L7-CL ;VL3-L7-CH1-L8-CL;VL3-L7-CL-L8-CH1;VL3-L7-CH1-L8-Fc;VL3-L7-CL-L8-Fc;VL3-L7-CH1-L8-CL-Fc;VL3-L7-CL-L8-CH1-Fc;VL3-L7-CH1-L8-CL -L9-Fc; or VL3-L7-CL-L8-CH1-L9-Fc by VL3-L7-CL-L8-CH1-L9-Fc;VH3-CH1-CL-Fc;VH3-CL-CH1-Fc;VH3-L10-Fc;VH3-L10-CH1;VH3-L10-CL;VH3-L10-CH1-L11-CL;V H3-L10-CL-L11-CH1;VH3-L10-CH1-L11-Fc;VH3-L10-CL-L11-Fc;VH3-L10-CH1-L11-CL-Fc;VH3-L1 VH3-L10-CH1-L11-CL-L12-Fc; or VH3-L10-CL-L11-CH1-L12-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein. VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, and L12 are amino acid linkers.

[0042] Provided herein are VL1-VL2-VL3-VH3-VH2-VH1; VH1-VH2-VH3-VL3-VL2-VL1; VL1-VH2-VL3-VH3-VL2-VH1; VH1-VL2-VH3-VL3-VH2-VL1; VL1-VL2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VL2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VH2-VH3-VL3-VL2-VH1; VH1-VL2-VL3-VH3-VL2-VH1; VH1-VL2-VL3-VH3-VL2-VH1; V L1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1;VL1-L1-VH2-L2-VL3-L3-VH3-L 4-VL2-L5-VH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1;VH1-L1-VH2-L 2-VL3-L3-VH3-L4-VL2-L5-VL1; VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1; or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein. VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, L3, L4, and L5 are amino acid linkers.

[0043] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VL3-VH3-VH2-VH1; VH1-VH2-VH3-VL3-VL2-VL1; VL1-VH2-VL3-VH3-VL2-VH1; VH1-VL2-VH3-VL3-VH2-VL1; VL1-VL2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VL2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VH2-VH3-VL3-VL2-VH1; VH1-VL2-VL3-VH3-VL2-VL1; VL1-VH2-VH3-VL3-VL2-VH1; VH1-VL2-VL3-VH3 -VH2-VL1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1;VH1-L1-VH2-L2 -VH3-L3-VL3-L4-VL2-L5-VL1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-V H1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1;VL1-L1-VL2-L2-VH3-L 3-VL3-L4-VH2-L5-VH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1;VL1 -L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1; or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1; the second polypeptide has a structure represented by VL4-VH4; VH4-VL4; VL4-L6-VH4; VH4-L6-VL4; VL4-VL5-VH5-VH4; VH4-VH5-VL5-VL4; VL4-L6-VL5-L7-VH5-L8-VH4; VH4-L6-VH5-L7-VL5-L8-VL4; VL4-VL5-VL6-VH6-VH5-VH4; H4-VH5-VH6-VL6-VL5-VL4;VL4-VH5-VL6-VH6-VL5-VH4;VH4-VL5-VH6-VL 6-VH5-VL4;VL4-VL5-VH6-VL6-VH5-VH4;VH4-VH5-VL6-VH6-VL5-VL4;VL4- VH5-VH6-VL6-VL5-VH4;VH4-VL5-VL6-VH6-VH5-VL4;VL4-L6-VL5-L7-VL6- L8-VH6-L9-VH5-L10-VH4;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4;VL4-L6-VL5-L7-VH6-L 8-VL6-L9-VH5-L10-VH4;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4;VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH 4; or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4; where VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL4 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein. VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH5 is a fifth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH6 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, L3, L4, L5, L6, L7, L8, L9, and L10 are amino acid linkers.

[0044] Provided herein is VL1-VL2-VL3-VH3-VH2-VH1-Fc;VH1-VH2-VH3-VL3-VL2-VL1 -Fc;VL1-VH2-VL3-VH3-VL2-VH1-Fc;VH1-VL2-VH3-VL3-VH2-VL1-Fc;VL1- VL2-VH3-VL3-VH2-VH1-Fc;VH1-VH2-VL3-VH3-VL2-VL1-Fc;VL1-VH2-VH3- VL3-VL2-VH1-Fc;VH1-VL2-VL3-VH3-VH2-VL1-Fc;VL1-L1-VL2-L2-VL3-L3 -VH3-L4-VH2-L5-VH1-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L 6-Fc;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc;VH1-L1-VH2-L2-V H3-L3-VL3-L4-VL2-L5-VL1-L6-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2- L5-VH1-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc;VH1-L1-V L2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4- VH2-L5-VL1-L6-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc;VL1 -L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc;VH1-L1-VH2-L2-VL3-L3 -VH3-L4-VL2-L5-VL1-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6 -Fc; VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc; VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-Fc; VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc; or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein;VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region that includes immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, and L6 are amino acid linkers;

[0045] Provided herein are VL1-VL2-VL3-VH3-VH2-VH1-Fc-Fc; VH1-VH2-VH3-VL3-VL2-VL1-Fc-Fc; VL1-VH2-VL3-VH3-VL2-VH1-Fc-Fc; VH1-VL2-VH3-VL3-VH2-VL1-Fc-Fc; VL1-VL2-VH3-VL3-VH2-VH1-Fc-Fc; VH1-VH2-VL3-VH3-VL2-VL1-Fc-Fc; VL1-VH2-VH3-VL3-VL2-VH1-Fc-Fc; VH1-VL2-VL3-VH3-VH2-VL1-Fc-Fc; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-Fc-Fc; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc-Fc; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc-L7-Fc; VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc-Fc; VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-Fc-Fc; VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-Fc-L7-Fc; VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-Fc-Fc; VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc-Fc; VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc-L7-Fc; VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc-Fc; VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc-Fc; VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc-L7-Fc; VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc-Fc; VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc-Fc; VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc-L7-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-Fc-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc-Fc;VH1-L1-V H2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc-L7-Fc;L1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc-Fc;VL1-L1-VH2-L2-V H3-L3-VL3-L4-VL2-L5-VH1-L6-Fc-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-Fc-L7-Fc;VH1-L1-VL2-L2-VL3 -L3-VH3-L4-VH2-L5-VL1-Fc-Fc;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc-Fc; or VH1-L1-VL2-L2-VL3-L3-VH an antigen-binding polypeptide having a structure represented by 3-L4-VH2-L5-VL1-L6-Fc-L7-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising an immunoglobulin heavy chain constant region 2 (CH2), an immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers;

[0046] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VL3-VH3-VH2-VH1-Fc; VH1-VH2-VH3-VL3-VL2-VL1-Fc; VL1-VH2-VL3-VH3-VL2-VH1-Fc; VH1-VL2-VH3-VL3-VH2-VL1-Fc; VL1-VL2-VH3-VL3-VH2-VH1-Fc; VL1-VL2-VH3-VL3-VH2-VH1-Fc; VH1-VH2-VL3-VH3-VL2-VH1-Fc; VH1-VH2-VL3-VH3-VL2-VH3-VL2-VL1-Fc; VL1-VH2-VH3-VL3-VH2-VH1-Fc; 1-Fc;VH1-VL2-VL3-VH3-VH2-VL1-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH 2-L5-VH1-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc;VH1-L 1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc;VH1-L1-VH2-L2-VH3-L3-VL3- L4-VL2-L5-VL1-L6-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-Fc; VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc;VH1-L1-VL2-L2-VH3 -L3-VL3-L4-VH2-L5-VL1-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL 1-L6-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc;VL1-L1-VL2-L 2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-V L2-L5-VL1-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc;VL1- L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc;VL1-L1-VH2-L2-VH3-L3-VL3 -L4-VL2-L5-VH1-L6-Fc;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc; or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc;The second polypeptide is Fc; VL4-VH4-Fc; VH4-VL4-Fc; VL4-L7-VH4-Fc; VH4-L7-VL4-Fc; VL4-L7-VH4-L8-Fc; VH4-L7-VL4-L8-Fc; VL4-VL5-VH5-VH4-Fc; VH4-VH5-VL5-VL4-Fc; VL4-L7-VL5-L8-VH5-L9-VH4-Fc; VH4-L7-VH5-L8-VL5-L9-VL4-Fc; VL4-L7-VL5-L8-VH5-L9-VH4-L10-Fc; VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc; VL4-VL5-VL6-VH6-VH5-VH4-Fc; VH4-VH5-VH6-VL6-VL5-VL4-Fc; VL4-VH5-VL6-VH6-VL5-VH4-Fc; VH4-VL5-VH6-VL6-VH5-VL4-Fc; VL4-VL5-VH6-VL6-VH5-VH4-Fc; VH4-VH5-VL6-VH6-VL5-VL4-Fc; VL4-VH5-VH6-VL6-VL5-VH4-Fc; VH4-VL5-VL6-VH6-VH5-VL4-Fc; VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc; VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc; VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc; VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc; VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc; VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc; VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc; VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc; VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc; VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc; VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc;VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc;VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc;VH4-L7-VH5-L 8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc;VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc; H6-L10-VH5-L11-VL4-L12-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL5 is a fifth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL6 is a sixth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein. VH5 is a fifth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH6 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region that includes immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, and L12 are amino acid linkers;

[0047] Provided herein are: VL1-VL2-VL3-VH3-VH2-VH1-CH1-CL; VL1-VL2-VL3-VH3-VH2-VH1-CL-CH1; VH1-VH2-VH3-VL3-VL2-VL1-CH1-CL; VH1-VH2-VH3-VL3-VL2-VL1-CL-CH1; VL1-VH2-VL3-VH3-VL2-VH1-CH1-CL; VL1-VH2-VL3-VH3-VL2-VH1-CL-CH1; VH1-VL2-VH3-VL3-VH2-VL1-CH1-CL; VH1-VL2-VH3-VL3-VH2-VL1-CL-CH1; VL1-VL2-VH3-VL3-VH2-VH1-CH1-CL; VL1-VL2-VH3-VL3-VH2-VH1-CL-CH1; VH1-VH2-VL3-VH3-VL2-VL1-CH1-CL; VH1-VH2-VL3-VH3-VL2-VL1-CL-CH1; VL1-VH2-VH3-VL3-VL2-VH1-CH1-CL; VL1-VH2-VH3-VL3-VL2-VH1-CL-CH1; VH1-VL2-VL3-VH3-VH2-VL1-CH1-CL; VH1-VL2-VL3-VH3-VH2-VL1-CL-CH1; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1-CL; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1-CL; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1-L7-CL; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL-CH1; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-CH1; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-L7-CH1; VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1-CL; VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1-CL; VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1-L7-CL; VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL-CH1;<h2 style=";text-align:left;direction:ltr">VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL-CH1;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL-L7-CH1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1-L7- CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-CH1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL-CH1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL-L7-CH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH1-CL;V H1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH1-L7-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-CH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-CH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-L7-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1-CL;VL 1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-L7-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1-CL;VH1-L1-VH2-L2-VL 3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-V L2-L5-VL1-L6-CH1-L7-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1- CL-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL-CH1;VH1-L1 -VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL-L7-CH1;VL1-L1-VH2-L2-VH 3-L3-VL3-L4-VL2-L5-VH1-CH1-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2- L5-VH1-L6-CH1-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1 -L7-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL-CH1;VL1-L1-VH2 -L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL-CH1;VL1-L1-VH2-L2-VH3-L3-VL 3-L4-VL2-L5-VH1-L6-CL-L7-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L 5-VL1-CH1-CL;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1-CL; VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1-L7-CL;VH1-L1-VL2 -L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL-CH1; VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CL-CH1; or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CL-L7-CH1; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein;VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is heavy chain constant region 1; CL is a light chain constant region; and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers;

[0048] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VL3-VH3-VH2-VH1-CH1; VL1-VL2-VL3-VH3-VH2-VH1-CL; VL1-VL2-VL3-VH3-VH2-VH1-CH1-CL; VL1-VL2-VL3-VH3-VH2-VH1-CL-CH1; VH1-VH2-VH3-VL3-VL2-VL1-CH1; VH1-VH2-VH3-VL3-VL2-VL1-CL; VH1-VH2-VH3-VL3-VL2-VL1-CL; VH1-VH2-VH3-VL 3-VL2-VL1-CH1-CL;VH1-VH2-VH3-VL3-VL2-VL1-CL-CH1;VL1-VH2-VL3-VH 3-VL2-VH1-CH1;VL1-VH2-VL3-VH3-VL2-VH1-CL;VL1-VH2-VL3-VH3-VL2-VH 1-CH1-CL;VL1-VH2-VL3-VH3-VL2-VH1-CL-CH1;VH1-VL2-VH3-VL3-VH2-VL 1-CH1;VH1-VL2-VH3-VL3-VH2-VL1-CL;VH1-VL2-VH3-VL3-VH2-VL1-CH1-CL ;VH1-VL2-VH3-VL3-VH2-VL1-CL-CH1;VL1-VL2-VH3-VL3-VH2-VH1-CH1;VL 1-VL2-VH3-VL3-VH2-VH1-CL;VL1-VL2-VH3-VL3-VH2-VH1-CH1-CL;VL1-VL2 -VH3-VL3-VH2-VH1-CL-CH1;VH1-VH2-VL3-VH3-VL2-VL1-CH1;VH1-VH2-VL 3-VH3-VL2-VL1-CL;VH1-VH2-VL3-VH3-VL2-VL1-CH1-CL;VH1-VH2-VL3-VH3 -VL2-VL1-CL-CH1;VL1-VH2-VH3-VL3-VL2-VH1-CH1;VL1-VH2-VH3-VL3-VL 2-VH1-CL;VL1-VH2-VH3-VL3-VL2-VH1-CH1-CL;VL1-VH2-VH3-VL3-VL2-VH1 -CL-CH1;VH1-VL2-VL3-VH3-VH2-VL1-CH1;VH1-VL2-VL3-VH3-VH2-VL1-CL ;VH1-VL2-VL3-VH3-VH2-VL1-CH1-CL;VH1-VL2-VL3-VH3-VH2-VL1-CL-CH1;<h2 style=";text-align:left;direction:ltr">VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1-CL;VL1-L1-VL2-L2-VL3-L3-VH 3-L4-VH2-L5-VH1-L6-CH1-CL;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1-L7-CL;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL-CH1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-CH1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-L7-CH1;VH1-L1-VH2-L2-VH3-L3- VL3-L4-VL2-L5-VL1-CH1;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1 -CL;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1-L7-CL;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL-CH1;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL-CH1;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL-L7-CH1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1;<h2 style=";text-align:left;direction:ltr">VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1-CL;VL1-L1-VH2-L2-VL3- L3-VH3-L4-VL2-L5-VH1-L6-CH1-L7-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-CH1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL-CH1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL-L7-CH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1;VH1-L1-VL2-L2-VH3-L3-VL 3-L4-VH2-L5-VL1-L6-CH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH1-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6 -CH1-L7-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-CH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-CH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-L7-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1;<h2 style=";text-align:left;direction:ltr">VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-L7-CL;VL1-L1-VL2- L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-L7-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1;VH1-L1-VH2-L2-VL3-L3- VH3-L4-VL2-L5-VL1-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-L7-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2- L5-VL1-CL-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL-L7-CH1;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL;<h2 style=";text-align:left;direction:ltr">VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-L7-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL-CH1;VL1-L1-VH 2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL-CH1;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL-L7-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL;VH1-L1-VL2-L2-VL3-L3-VH3 -L4-VH2-L5-VL1-L6-CL;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-CL;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1-CL;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1-L7-CL;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L 5-VL1-L6-CL-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6- VL4-VH4-CL;VL4-VH 4-CH1-CL;VL4-VH4-CL-CH1;VH4-VL4-CH1;VH4-VL4-CL;VH4-VL4-CH1-CL;VH4-VL4-CL-CH1;VL4-L8-VH4-CH1;VL4-L8-VH4-CL;VL4-L8-VH4-CH1-CL;VL4-L8-VH4-CL-CH1;VH4-L8-VL4-CH1;VH4-L8-VL4-CL;VH4-L8-VH4-CH1-CL;VH4-L8-VH4-CL-CH1;VL4-VL5-VH5-VH4-CH1;VL4-VL5-VH5-VH4-CL;VL4-VL5-VH5-VH4-CH1-CL;VL4-VL5-VH5-VH4-CL-CH1;VH4-VH5-VL5-V; L4-CH1;VH4-VH5-VL5-VL4-CL;VH4-VH5-VL5-VL4-CH1-CL;VH4-VH5-VL5-VL4-CL-CH1;VL4-L8-VL5-L9-VH5-L10-VH4-CH1;VL4-L8-VL5-L9-VH5-L10-VH4-CL;VL4-L8-VL5-L9-VH5-L10-VH4-CH1-CL;VL4-L8-VL5-L9-VH5-L10-VH4-CL-CH1;VH4-L8-VH5-L9-VL5-L10-VL4-CH1;VH4-L8-VH5-L9-VL5-L10-VL4-CL;VH4-L8-VH5-L9-VL5-L10-VL4-CH1-CL;VH4-L8-VH5-L9-VL5-L10-VL4-CL-CH1;VL4-VL5-VL6-VH6-VH5-VH4-CH1;VL4-VL5-VL6-VH6-VH5-VH4-CL;VL4-VL5-VL6-VH6-VH5-VH4-CH1-CL;VL4-VL5-VL6-VH6-VH5-VH4-CL-CH1;VH4-VH5-VH6-VL6-VL5-VL4-CH1;VH4-VH5-VH6-VL6-VL5-VL4-CL;VH4-VH5-VH6-VL6-VL5-VL4-CH1-CL;VH4-VH5-VH6-VL6-VL5-VL4-CL-CH1;VL4-VH5-VL6-VH6-VL5-VH4-CH1;VL4-VH5-VL6-VH6-VL5-VH4-CL;VL4-VH5-VL6-VH6-VL5-VH4-CH1-CL;VL4-VH5-VL6-VH6-VL5-VH4-CL-CH1;VH4-VL5-VH6-VL6-VH5-VL4-CH1;VH4-VL5-VH6-VL6-VH5-VL4-CL;VH4-VL5-VH6-VL6-VH5-VL4-CH1-CL;VH4-VL5-VH6-VL6-VH5-VL4-CL-CH1;VL4-VL5-VH6-VL6-VH5-VH4-CH1;VL4-VL5-VH6-VL6-VH5-VH4-CL;VL4-VL5-VH6-VL6-VH5-VH4-CH1-CL;VL4-VL5-VH6-VL6-VH5-VH4-CL-CH1;VH4-VH5-VL6-VH6-VL5-VL4-CH1;VH4-VH5-VL6-VH6-VL5-VL4-CL;VH4-VH5-VL6-VH6-VL5-VL4-CH1-CL;VH4-VH5-VL6-VH6-VL5-VL4-CL-CH1;VL4-VH5-VH6-VL6-VL5-VH4-CH1;VL4-VH5-VH6-VL6-VL5-VH4-CL;VL4-VH5-VH6-VL6-VL5-VH4-CH1-CL;VL4-VH5-VH6-VL6-VL5-VH4-CL-CH1;VH4-VL5-VL6-VH6-VH5-VL4-CH1;VH4-VL5-VL6-VH6-VH5-VL4-CL;VH4-VL5-VL6-VH6-VH5-VL4-CH1-CL;VH4-VL5-VL6-VH6-VH5-VL4-CL-CH1;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CH1;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CL;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CH1-CL;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CL-CH1;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CH1;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CL;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CH1-CL;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CL-CH1;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CH1;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CL;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CH1-CL;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CL-CH1;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CH1;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CL;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CH1-CL;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CL-CH1;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CH1;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CL;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CH1-CL;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CL-CH1;VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-CH1;VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-CL;VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-CH1-CL;VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-CL-CH1;VL4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VH4-CH1;VL4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VH4-CL;VL4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VH4-CH1-CL;VL4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VH4-CL-CH1;VH4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-CH1;VH4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-CL;VH4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-CH1-CL;VH4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-CL-CH1;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CH1;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CL;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CH1-CL;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CL-CH1;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CH1;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CL;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CH1-CL;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CL-CH1;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CH1;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CL;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CH1-CL;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CL-CH1;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CH1;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CL;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CH1-CL;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CL-CH1;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-L13-CH1;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-L13-CL;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-L13-CH1-CL;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-L13-CL-CH1;VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CH1;VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CL;VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CH1-CL;VH4-L8-V H5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CL-CH1;VL4-L8-VH5-L9-VH 6-L10-VL6-L11-VL5-L12-VH4-L13-CH1;VL4-L8-VH5-L9-VH6-L10-VL6-L 11-VL5-L12-VH4-L13-CL;VL4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VH 4-L13-CH1-CL;VL4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VH4-L13-CH 1;VH4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-L13-CH1;VH4-L8-VL 5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-L13-CL;VH4-L8-VL5-L9-VL6-L10 -VH6-L11-VH5-L12-VL4-L13-CH1-CL; or VH4-L8-VL5-L9-VL6-L10-VH6-L 11-VH5-L12-VL4-L13-CL-CH1; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL5 is a fifth immunoglobulin light chain variable region that specifically binds to an HIV protein; L6 is a sixth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and VH5 is a fifth immunoglobulin heavy chain variable region that specifically binds to an HIV protein;VH6 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is heavy chain constant region 1; CL is a light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, and L13 are amino acid linkers.

[0049] What is provided in this specification is an antigen-binding polypeptide complex containing polypeptide 1 and polypeptide 2; polypeptide 1 is VL1-VL2-VL3-VH3-VH2-VH1-CH1-Fc; ;VL1-VH2-VL3-VH3-VL2-VH1-CH1-Fc;VH1-VL2-VH3-VL3-VH2-VL1-CH1-Fc;VL1-VL2-VH3-VL3-VH2-VH1-CH1-Fc;VH1-VH2-VL3-VH3-VL2-VL1-CH1-Fc ;VL1-VH2-VH3-VL3-VL2-VH1-CH1-Fc;VH1-VL2-VL3-VH3-VH2-VL1-CH1-Fc;VL1-VL2-VL3-VH3-VH2-VH1-CL-Fc;VH1-VH2-VH3-VL3-VL2-VL1-CL-Fc;V L1-VH2-VL3-VH3-VL2-VH1-CL-Fc;VH1-VL2-VH3-VL3-VH2-VL1-CL-Fc;VL1-VL2-VH3-VL3-VH2-VH1-CL-Fc;VH1-VH2-VL3-VH3-VL2-VL1-CL-Fc;VL1-V H2-VH3-VL3-VL2-VH1-CL-Fc;VH1-VL2-VL3-VH3-VH2-VL1-CL-Fc;VL1-VL2-VL3-VH3-VH2-VH1-CH1-CL-Fc;VH1-VH2-VH3-VL3-VL2-VL1-CH1-CL-Fc;V L1-VH2-VL3-VH3-VL2-VH1-CH1-CL-Fc;VH1-VL2-VH3-VL3-VH2-VL1-CH1-CL-Fc;VL1-VL2-VH3-VL3-VH2-VH1-CH1-CL-Fc;VH1-VH2-VL3-VH3-VL2-VL1 -CH1-CL-Fc;VL1-VH2-VH3-VL3-VL2-VH1-CH1-CL-Fc;VH1-VL2-VL3-VH3-VH2-VL1-CH1-CL-Fc;VL1-VL2-VL3-VH3-VH2-VH1-CL-CH1-Fc;VH1-VH2-VH3 -VL3-VL2-VL1-CL-CH1-Fc;VL1-VH2-VL3-VH3-VL2-VH1-CL-CH1-Fc;VH1-VL2-VH3-VL3-VH2-VL1-CL-CH1-Fc;VL1-VL2-VH3-VL3-VH2-VH1-CL-CH1-Fc;<h2 style=";text-align:left;direction:ltr">VH1-VH2-VL3-VH3-VL2-VL1-CL-CH1-Fc;VL1-VH2-VH3-VL3-VL2-VH1-CL-CH1-Fc;VH1-VL2-VL3-VH3-VH2-VL1-CL-CH1-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1-Fc;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1-Fc;VL1-L1-VH2-L2-VL3-L3-VL3-L4-VL2-L5-VH1-CH1-Fc;VH1- L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-Fc;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-Fc;VL1-L1-VL2-L2-VL3- L3-VH3-L4-VH2-L5-VH1-CL-Fc;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL 1-CL-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL-Fc;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1-CL-Fc;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1-CL-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-CL-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-CL-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1-CL-Fc;VH1-L1-VH2-L2-VL3-L3-VH3- L4-VL2-L5-VL1-CH1-CL-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-CL-Fc;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-CL-Fc;V L1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL-CH1-Fc;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL-CH1-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L 4-VL2-L5-VH1-CL-CH1-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-CH1-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-CH1-Fc;VH1 -L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CL-CH1-Fc; VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL-CH1-Fc; orVH1-L1-VL2-L2-VL3-L3-VH3- L4-VH2-L5-VL1-CL-CH1-Fc has the structure shown by; CH1-Fc;VH4-VL4-CL-Fc;VH4-VL4-CH1-CL-Fc;VH4-VL4-CL-CH1-Fc;VL4-L6-VH4-CH1-Fc;VL4-L6-VH4-CL-Fc;VL4-L6-VH4-CH1-CL-Fc;VL4-L6-VH4 -CL-CH1-Fc;VH4-L6-VL4-CH1-Fc;VH4-L6-VL4-CL-Fc;VH4-L6-VL4-CH1-CL-Fc;VH4-L6-VL4-CL-CH1-Fc;VL4-CL-VH4-CH1-Fc;VH4-CL-VL4-CH1-Fc;<h2 style=";text-align:left;direction:ltr">VL4-CH1-VH4-CL-Fc;VH4-CH1-VL4-CL-Fc;VL4-L6-CL-L7-VH4-L8-CH1-Fc;VL4-L6-CL-L7-VH4-L8-CH1-L9-Fc;VH4-L6-CL-L7-VL4-L8-CH1-Fc;VH4-L6-CL-L7-VL4-L8-CH1-L9-Fc;VL4-L6-CH1-L7-VH4-L8-CL-Fc;VL4-L6-CH1-L7-VH4-L8-CL-Fc;VL4-L6-CH1-L7-VH4-L8-CL-L9-Fc;VH4-L6-CH1-L7-VL4-L8-CL-Fc;VH4-L6-CH1-L7 L7-VL4-L8-CL-L9-Fc;VL4-VL5-VH5-VH4-CH1-Fc;VL4-VL5-VH5-VH4-CL-Fc;VL4-VL5-VH5-VH4-CH1-CL-Fc;VL4-VL5-VH5-VH4-CL-CH1-Fc;VH4-VH5 VL5-VL4-CH1-Fc;VH4-VH5-VL5-VL4-CL-Fc;VH4-VH5-VL5-VL4-CH1-CL-Fc;VH4-VH5-VL5-VL4-CL-CH1-Fc; L4-L6-VL5-L7-VH5-L8-VH4-CL-Fc;VL4-L6-VL5-L7-VH5-L8-VH4-CH1-CL-Fc;VL4-L6-VL5-L7-VH5-L8-VH4-CL-CH1-Fc;VH4-L6-VH5-L7-VL5-L8-VL4-CH1-Fc;VH4-L6-VH5-L7-VL5-L8-VL4-CH1-Fc;VH4-L6-VH5-L7-VL5-L8-VL4-CL-Fc;VH4-L6-VH5-L7-VL5-L8-VL4-CH1-CL-Fc;VH4-L6-VH5-L7-VL5-L8-VL4-CH1-CL-Fc;VH4-L6-VH5-L7-VL5-L8-VL4-CL-CH1-Fc;VL4-VL5-VL6- VH6-VH5-VH4-CH1-Fc;VL4-VL5-VL6-VH6-VH5-VH4-CL-Fc;VL4-VL5-VL6- VH6-VH5-VH4-CH1-CL-Fc;VL4-VL5-VL6-VH6-VH5-VH4-CL-CH1-Fc;VH4-VH 5-VH6-VL6-VL5-VL4-CH1-Fc;VH4-VH5-VH6-VL6-VL5-VL4-CL-Fc;VH4-VH 5-VH6-VL6-VL5-VL4-CH1-CL-Fc;VH4-VH5-VH6-VL6-VL5-VL4-CL-CH1-Fc;VL4-VH5-VL6-VH6-VL5-VH4-CH1-Fc;VL4-VH5-VL6-VH6-VL5-VH4-CL-Fc;VL4-VH5-VL6-VH6-VL5-VH4-CH1-CL-Fc;VL4-VH5-VL6-VH6-VL5-VH4-CL-CH1-Fc;VH4-VL5-VH6-VL6-VH5-VL4-CH1-Fc;VH4-VL5-VH6-VL6-VH5-VL4-CL-Fc;VH4-VL5-VH6-VL6-VH5-VL4-CH1-CL-Fc;VH4-VL5-VH6-VL6-VH5-VL4-CL-CH1-Fc;VL4-VL5-VH6-VL6-VH5-VH4-CH1-Fc;VL4-VL5-VH6-VL6-VH5-VH4-CL-Fc;VL4-VL5-VH6-VL6-VH5-VH4-CH1-CL-Fc;VL4-VL5-VH6-VL6-VH5-VH4-CL-CH1-Fc;VH4-VH5-VL6-VH6-VL5-VL4-CH1-Fc;VH4-VH5-VL6-VH6-VL5-VL4-CL-Fc;VH4-VH5-VL6-VH6-VL5-VL4-CH1-CL-Fc;VH4-VH5-VL6-VH6-VL5-VL4-CL-CH1-Fc;VL4-VH5-VH6-VL6-VL5-VH4-CH1-Fc;VL4-VH5-VH6-VL6-VL5-VH4-CL-Fc;VL4-VH5-VH6-VL6-VL5-VH4-CH1-CL-Fc;VL4-VH5-VH6-VL6-VL5-VH4-CL-CH1-Fc;VH4-VL5-VL6-VH6-VH5-VL4-CH1-Fc;VH4-VL5-VL6-VH6-VH5-VL4-CL-Fc;VH4-VL5-VL6-VH6-VH5-VL4-CH1-CL-Fc;VH4-VL5-VL6-VH6-VH5-VL4-CL-CH1-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CH1-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CL-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CH1-CL-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CL-CH1-Fc;<h2 style=";text-align:left;direction:ltr">VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CH1-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CL-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CH1-CL-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CL-CH1-Fc;VL4-L6-VH5-L7-VH6-L8-;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">VH6-L9-VL5-L10-VH4-CH1-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-CL-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-CH1-CL-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-CL-CH1-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CH1-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9- VH5-L10-VL4-CL-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CH1-CL-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CL-CH1-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CH1-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CH1-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CL-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CL-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CL-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-V H4-CH1-CL-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CL-CH1-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CH1-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CL-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CL-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CH1-CL-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CL -CH1-Fc;VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CH1-Fc;VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CL-Fc;VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CH1-CL-Fc;VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CH1-CL-Fc;VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CL-CH1-Fc;VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CH1-Fc;<h2 style=";text-align:left;direction:ltr">VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CL-Fc;VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CH1-CL-Fc;VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CL-CH1-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CL-CH1-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CH1-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CL-F c;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CH1-CL-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CL-CH1-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CH1-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CH1-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10 -VL4-L11-CH1-CL-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CL-CH1-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CH1-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CH1-CL-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CL-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CL-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CH1-CL-Fc;VL4-L6-VH5-L7-VL6 -L8-VH6-L9-VL5-L10-VH4-L11-CL-CH1-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-L11-CH1-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-L11-CL-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-L11-CL-CH1-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-L11-CL-CH1-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-L11-CH1-Fc;VL4-L6-VL 5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-L11-CL-Fc;VL4-L6-VL5-L7-VH6-L8 -VL6-L9-VH5-L10-VH4-L11-CH1-CL-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9 -VH5-L10-VH4-L11-CL-CH1-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L1 0-VL4-L11-CH1-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-L11- CL-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-L11-CH1-CL-Fc;V H4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-L11-CL-CH1-Fc;VL4-L6-V H5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-L11-CH1-Fc;VL4-L6-VH5-L7-VH6- L8-VL6-L9-VL5-L10-VH4-L11-CL-Fc;VL4-L6-VH5-L7-VH6-L8-VL6-L9-V L5-L10-VH4-L11-CH1-CL-Fc;VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10- VH4-L11-CL-CH1-Fc;VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11 -CH1-Fc;VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11-CL-Fc;VH4 -L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11-CH1-CL-Fc; or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11-CL-CH1-Fc; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein;VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL5 is a fifth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL6 is a sixth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and VH4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein. VH5 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH6 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is heavy chain constant region 1; CL is a light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, and L11 are amino acid linkers;

[0050] VL1-VL2-VL3-VH3-VH2-VH1-CH3-CH3; VH1-VH2-VH3-VL3-VL2-VL1-CH3-CH3; VL1-VH2-VL3-VH3-VL2-VH1-CH3-CH3; VH1-VL2-VH3-VL3-VH2-VL1-CH3-CH3; VL1-VL2-VH3-VL3-VH2-VH1-CH3-CH3; VH1-VH2-VL3-VH3-VL2-VL1-CH3-CH3; VL1-VH2-VH3-VL3-VL2-VH1-CH3-CH3; VH1-VL2-VL3-VH3-VH2-VL1-CH3-CH3; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH3-CH3; VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH3-CH3; VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH3-CH3; VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH3-CH3; VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH3-CH3; VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH3-CH3; VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH3-CH3; VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH3-CH3; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH3-CH3; VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH3-CH3; VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH3-CH3; VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH3-CH3; VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH3-CH3; VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH3-CH3; VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH3-CH3;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH3-CH3;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH3-L7 -CH3;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH3-L7-CH3;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L 6-CH3-L7-CH3;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH3-L7-CH3;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2- L5-VH1-L6-CH3-L7-CH3;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH3-L7-CH3;VL1-L1-VH2-L2-VH3-L3-VL3- or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH3-L7-CH3; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers;

[0051] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide is VL1-VL2-VL3-VH3-VH2-VH1; VH1-VH2-VH3-VL3-VL2-VL1; VL1-VH2-VL3-VH3-VL2-VH1; VH1-VL2-VH3-VL3-VH2-VL1; VL1-VL2-VH3-VL3-VH2-VH1; VH1-VL2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VL2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VH2-VH3-VL3-VL2-VH1; -VL3-VH3-VH2-VL1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1;VH1-L1 -VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-V L2-L5-VH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1;VL1-L1-VL2-L2 -VH3-L3-VL3-L4-VH2-L5-VH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-V L1; VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1; or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1; the second polypeptide has a structure represented by VL4-VL5; VL4-L6-VL5; VL4-VL5-VL6; VL4-L6-VL5-L7-VL6; VL4-CL; VL4-L6-CL; VL4-VL5-CL; VL4-L6-VL5-CL; VL4-L6-VL5-L7-CL; VL4-VL5-VL6-CL; VL4-L6-VL5-L7-VL6- CL; VL4-L6-VL5-L7-VL6-L8-CL; VL4-CH1; VL4-L6-CH1; VL4-VL5-CH1; VL4-L6-VL5-CH1; VL4-L6-VL5-L7-CH1; VL4-VL5-VL6-CH1; VL4-L6-VL5-L7-VL6-CH1; or VL4-L6-VL5-L7-VL6-L8-CH1; the third polypeptide has a structure represented by VH4-VH5; VH4-L9-VH5; VH4-VH5-VH6; VH4-L9-VH5-L10-VH6; VH4-CH1; VH4-L9-CH1;VH4-VH5-CH1;VH4-L9-VH5-CH1;VH4-L9-VH5-L10-CH1;VH4-VH5-VH6-CH1;VH4-L9-VH5-L10-VH6-CH1;VH4-L9-VH5-L10-VH 6-L11-CH1;VH4-CL;VH4-L9-CL;VH4-VH5-CL;VH4-L9-VH5-CL;VH4-L9-VH5-L10-CL;VH4-VH5-VH6-CL;VH4-L9-VH5-L10-VH6 -CL; or VH4-L9-VH5-L10-VH6-L11-CL; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein. VL5 is a fifth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL6 is a sixth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH5 is a fifth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH6 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is heavy chain constant region 1; CL is a light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, and L11 are amino acid linkers.

[0052] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide is VL1-VL2-VL3-VH3-VH2-VH1-Fc; VH1-VH2-VH3-VL3-VL2-VL1-Fc; VL1-VH2-VL3-VH3-VL2-VH1-Fc; VH1-VL2-VH3-VL3-VH2-VL1-Fc; VL1-VL2-VH3-VL3-VH2-VH1-Fc; VL1-VL2-VH3-VL3-VH2-VH1-Fc; VH1-VH2-VL3-VH3-VL2-VL1-Fc; VH1-VH2-VL3-VH3-VL2-VL1-Fc; VL1-VH2-VH3-VL3-VH2-VH1-Fc; VH1-VH2-VL3-VH3-VL2-VL1-Fc; VL1-VH2-VH3-VL3 -VL2-VH1-Fc;VH1-VL2-VL3-VH3-VH2-VL1-Fc;VL1-L1-VL2-L2-VL3-L3-VH 3-L4-VH2-L5-VH1-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc ;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc;VH1-L1-VH2-L2-VH3-L 3-VL3-L4-VL2-L5-VL1-L6-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH 1-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc;VH1-L1-VL2-L 2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L 5-VL1-L6-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc;VL1-L1-V L2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L 4-VL2-L5-VL1-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc;V L1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc;VL1-L1-VH2-L2-VH3-L3-V L3-L4-VL2-L5-VH1-L6-Fc;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-F c; or having a structure represented by VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc;The second polypeptide is VL4-VL5;VL4-L7-VL5;VL4-CL;VL4-L7-CL;VL4-CH1;VL4-L7-CH1;VH4-VH5;VH4-L7-VH5;VH4-CL;VH4-L7-CL;VH4-CH1;VH4-L7-CH1;VL4-VL5-VL6;VL4-L7-VL5-L8-VL6;VL4-VL5-VL6-CL;VL4-L7-VL5-L8-VL6-CL;VL4-L7-VL5-L8-VL6-CL;VL4-L7-VL5-L8-VL6-L9-CL;VL4-VL5-VL6-CH1;VL4-L7-VL5-L8-VL6-CH1;V and the third polypeptide has a structure represented by VH4-VH5-Fc; VH4-L10-VH5-Fc; VH4-L10-VH5-L11-Fc; VH 4-CH1-Fc;VH4-L10-CH1-Fc;VH4-L10-CH1-L11-Fc;VH4-CL-Fc;VH4-L10-C L-Fc;VH4-L10-CL-L11-Fc;VH4-VH5-Fc;VH4-L10-VH5-Fc;VH4-L10-VH5-L 11-Fc;VH4-VH5-VH6-Fc;VH4-L10-VH5-L11-VH6-Fc;VH4-L10-VH5-L11-VH 6-L12-Fc;VH4-VH5-VH6-CH1-Fc;VH4-L10-VH5-L11-VH6-CH1-Fc;VH4-L10- VH5-L11-VH6-L12-CH1-Fc;VH4-L10-VH5-L11-VH6-L12-CH1-L13-Fc;VH4- VH5-VH6-CL-Fc;VH4-L10-VH5-L11-VH6-CL-Fc;VH4-L10-VH5-L11-VH6-L12 -CL-Fc;VH4-L10-VH5-L11-VH6-L12-CL-L13-Fc;VL4-VL5-VL6-Fc;VL4-L1 0-VL5-L11-VL6-Fc;VL4-L10-VL5-L11-VL6-L12-Fc;VL4-VL5-VL6-CH1-Fc;VL4-L10-VL5-L11-VL6-CH1-Fc; VL4-L10-VL5-L11-VL6-L12-CH1-Fc; VL4-L10-VL5-L11-VL6-L12-CH1-L13-Fc; VL4-VL5-VL6-CL-Fc; VL4-L10-VL5-L11-VL6-CL-Fc; VL4-L10-VL5-L11-VL6-L12-CL-Fc; or VL4-L10-VL5-L11-VL6-L12-CL-L13-Fc. VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL5 is a fifth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL6 is a sixth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH5 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH6 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region that includes immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is heavy chain constant region 1; CL is a light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, and L13 are amino acid linkers;

[0053] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide is VL1-VL2-VL3-VH3-VH2-VH1-Fc; VH1-VH2-VH3-VL3-VL2-VL1-Fc; VL1-VH2-VL3-VH3-VL2-VH1-Fc; VH1-VL2-VH3-VL3-VH2-VL1-Fc; VL1-VL2-VH3-VL3-VH2-VH1-Fc; VL1-VL2-VH3-VL3-VH2-VH1-Fc; VH1-VH2-VL3-VH3-VL2-VL1-Fc; VH1-VH2-VL3-VH3-VL2-VL1-Fc; VL1-VH2-VH3-VL3-VH2-VH1-Fc; VH1-VH2-VL3-VH3-VL2-VL1-Fc; VL1-VH2-VH3-VL3 -VL2-VH1-Fc;VH1-VL2-VL3-VH3-VH2-VL1-Fc;VL1-L1-VL2-L2-VL3-L3-VH 3-L4-VH2-L5-VH1-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc ;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc;VH1-L1-VH2-L2-VH3-L 3-VL3-L4-VL2-L5-VL1-L6-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH 1-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc;VH1-L1-VL2-L 2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L 5-VL1-L6-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc;VL1-L1-V L2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L 4-VL2-L5-VL1-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc;V L1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc;VL1-L1-VH2-L2-VH3-L3-V L3-L4-VL2-L5-VH1-L6-Fc;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-F c; or having a structure represented by VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc;The second polypeptide is VL4-VL5-Fc;VL4-L7-VL5-Fc;VL4-L7-VL5-L8-Fc;VL4-CL-Fc;VL4-L7-CL-Fc;VL4-L7-CL-L8-Fc;VL4-CH1-Fc;VL4-L7-CH1-Fc;VL4-L7- CH1-L8-Fc;VH4-VH5-Fc;VH4-L7-VH5-Fc;VH4-L7-VH5-L8-Fc;VH4-CL-Fc; VH4-L7-CL-Fc;VH4-L7-CL-L8-Fc;VH4-CH1-Fc;VH4-L7-CH1-Fc;VH4-L7-C H1-L8-Fc;VL4-VL5-VL6-Fc;VL4-L7-VL5-L8-VL6-Fc;VL4-L7-VL5-L8-VL 6-L9-Fc;VL4-VL5-VL6-CL-Fc;VL4-L7-VL5-L8-VL6-CL-Fc;VL4-L7-VL5-L 8-VL6-L9-CL-Fc;VL4-L7-VL5-L8-VL6-L9-CL-L10-Fc;VL4-VL5-VL6-CH1- Fc;VL4-L7-VL5-L8-VL6-CH1-Fc;VL4-L7-VL5-L8-VL6-L9-CH1-Fc;VL4-L7 -VL5-L8-VL6-L9-CH1-L10-Fc;VH4-VH5-VH6-Fc;VH4-L7-VH5-L8-VH6-Fc ;VH4-L7-VH5-L8-VH6-L9-Fc;VH4-VH5-VH6-CL-Fc;VH4-L7-VH5-L8-VH6-C L-Fc;VH4-L7-VH5-L8-VH6-L9-CL-Fc;VH4-L7-VH5-L8-VH6-L9-CL-L10-Fc ;VH4-VH5-VH6-CH1-Fc;VH4-L7-VH5-L8-VH6-CH1-Fc;VH4-L7-VH5-L8-VH6 -L9-CH1-Fc; or VH4-L7-VH5-L8-VH6-L9-CH1-L10-Fc; the third polypeptide has a structure represented by VH4-VH5; VH4-L11-VH5; VH4-CH1; VH4-L11-CH1; VH4-CL; VH4-L11-CL; VH4-VH5; VH4-L11-VH5; VH4-VH5-VH6; VH4-L11-VH5-L12-VH6; VH4-VH5-VH6-CH1; VH4-L11-VH5-L12-VH6-CH1; VH4-L11-VH5-L12-VH6-CH1; VH4-L11-VH5-L12-VH6-L13-CH1;VH4-VH5-VH6-CL;VH4-L11-VH5-L12-VH6-CL;VH4-L11-VH5-L12-VH6-L13-CL;VL4-VL5-VL6;VL4-L11-VL5-L12-VL6;VL4-VL5-VL6-CH 1;VL4-L11-VL5-L12-VL6-CH1;VL4-L11-VL5-L12-VL6-L13-CH1;VL4-VL5-VL6-CL;VL4-L11-VL5-L12-VL6-CL; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL5 is a fifth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL6 is a sixth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH5 is a sixth immunoglobulin light chain variable region that specifically binds to an HIV protein. VH6 is a fifth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH7 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is heavy chain constant region 1; CL is a light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, and L13 are amino acid linkers;

[0054] In some embodiments, the HIV protein to which the heavy and light chain variable regions specifically bind is an HIV envelope protein, an HIV structural protein, an HIV functional protein, or an HIV accessory protein. In other embodiments, the HIV envelope protein is an HIV envelope glycoprotein (Env), an HIV envelope glycoprotein gp160, an HIV envelope surface glycoprotein gp120, or an HIV transmembrane envelope protein gp41. In other embodiments, the HIV structural protein is p17, p24, p7, or p55. In other embodiments, the HIV functional protein is p66, HIV-1 protease (PR), or p31. In other embodiments, the HIV accessory protein is Nef, Tat, Rev, Vif, Vpr, or Vpu.

[0055] Provided herein is an antibody or antigen-binding fragment thereof comprising an antigen-binding polypeptide or antigen-binding polypeptide complex described herein.

[0056] Provided herein are polypeptides having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 32-47, 84, 86, 88, 90, 92, 94, 96, and 98. Also provided herein are polypeptides encoded by polynucleotides having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 48-59, 85, 87, 89, 91, 93, 95, 97, and 99.

[0057] Provided herein are polynucleotides that encode an antigen-binding polypeptide or antigen-binding polypeptide complex described herein. Also provided herein are polynucleotides that have at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 48-59, 85, 87, 89, 91, 93, 95, 97, and 99. Also provided herein are polynucleotides that encode a polypeptide that has at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 32-47, 84, 86, 88, 90, 92, 94, 96, and 98.

[0058] Provided herein are vectors comprising the polynucleotides described herein.

[0059] Provided herein are host cells containing the polynucleotides or vectors described herein.

[0060] Provided herein is a chimeric antigen receptor (CAR) comprising an antigen-binding polypeptide or antigen-binding polypeptide complex described herein.

[0061] Provided herein is an immune cell that comprises a CAR described herein.

[0062] Provided herein is a pharmaceutical composition comprising (i) an antigen-binding polypeptide or antigen-binding polypeptide complex, an antibody or antigen-binding fragment thereof, a polypeptide, a polynucleotide, a vector, a host cell, a CAR or immune cell, or a combination thereof, as described herein, and (ii) a pharmaceutically acceptable carrier.

[0063] Provided herein are kits that include an antigen-binding polypeptide or antigen-binding polypeptide complex, an antibody or antigen-binding fragment thereof, a polypeptide, a polynucleotide, a vector, a host cell, a CAR, an immune cell, or a pharmaceutical composition described herein, or a combination thereof.

[0064] Provided herein are methods of treating or preventing a Human Immunodeficiency Virus (HIV) infection, comprising administering to a subject in need of treatment or prevention of a Human Immunodeficiency Virus (HIV) infection a therapeutically effective amount of an antigen-binding polypeptide or antigen-binding polypeptide complex, an antibody or antigen-binding fragment thereof, a polypeptide, a polynucleotide, a vector, a host cell, a CAR, an immune cell, or a pharmaceutical composition, or combination thereof, described herein.

[0065] Provided herein are methods for treating or preventing Acquired Immune Deficiency Syndrome (AIDS), comprising administering to a subject in need of treatment or prevention of Acquired Immune Deficiency Syndrome (AIDS) a therapeutically effective amount of an antigen-binding polypeptide or antigen-binding polypeptide complex, an antibody or antigen-binding fragment thereof, a polypeptide, a polynucleotide, a vector, a host cell, a CAR, an immune cell, or a pharmaceutical composition, or combination thereof, described herein.

[0066] Provided herein are methods of treating or preventing AIDS-related complex (ARC), comprising administering to a subject in need of treatment or prevention of AIDS-related complex (ARC), a therapeutically effective amount of an antigen-binding polypeptide or antigen-binding polypeptide complex, an antibody or antigen-binding fragment thereof, a polypeptide, a polynucleotide, a vector, a host cell, a CAR, an immune cell, or a pharmaceutical composition, or combination thereof, described herein.

[0067] Provided herein are methods of treating or preventing an HIV-associated opportunistic infection, comprising administering to a subject in need of treatment or prevention of an HIV-associated opportunistic infection a therapeutically effective amount of an antigen-binding polypeptide or antigen-binding polypeptide complex, an antibody or antigen-binding fragment thereof, a polypeptide, a polynucleotide, a vector, a host cell, a CAR, an immune cell, or a pharmaceutical composition, or combination thereof, as described herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0068] Detailed Description of the Invention The present invention is directed to antigen-binding polypeptides and antigen-binding polypeptide complexes (e.g., antibodies or antigen-binding fragments thereof) with improved characteristics. In some embodiments, the present invention allows for the generation of multispecific and multifunctional antigen-binding polypeptides and antigen-binding polypeptide complexes through the expression of complementary self-assembled heavy and light chains expressed in a single polypeptide per arm, and optionally by the addition of specific amino acid linkers. Due to this multifunctionality, the antigen-binding polypeptides and antigen-binding polypeptide complexes of the present invention can bind to specific combinations of target molecules for selectivity or broadness / neutralization, can bring together two or more cell types, can deliver activation signals to targets together, can modify the disease microenvironment, and can enhance the avidity of the binding for improved efficacy.

[0069] Throughout the specification and claims, various terms relating to aspects of the present disclosure are used. Unless otherwise indicated, such terms are to be given their ordinary meaning in the art. Other terms that are specifically defined are to be interpreted in a manner consistent with the definitions set forth herein.

[0070] definition As used herein, the term "antigen-binding polypeptide" refers to a polypeptide capable of specifically binding to one or more substances (i.e., one or more antigens or epitopes) that induce an immune response.

[0071] As used herein, the term "antigen-binding polypeptide complex" refers to a group of two, three, four, or more related polypeptides, where at least one polypeptide has the ability to specifically bind to one or more antigens. Antigen-binding polypeptide complexes include, but are not limited to, antibodies or antigen-binding fragments thereof.

[0072] The term "antibody" includes, but is not limited to, a glycoprotein immunoglobulin that specifically binds to an antigen and comprises at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each H chain comprises a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. The heavy chain constant region comprises three constant domains, CH1, CH2, and CH3. Each light chain comprises a light chain variable region (abbreviated herein as VL) and a light chain constant region. The light chain constant region comprises one constant domain, CL. The VH and VL regions can be further subdivided into regions of hypervariability, called complementarity determining regions (CDRs), interspersed with more conserved regions, called framework regions (FRs). Each VH and VL is composed of three CDRs and four FRs, arranged from amino terminus to carboxy terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain binding domains that interact with antigens. The constant regions of the antibody may mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system. The heavy chain may or may not have a C-terminal lysine. Unless otherwise specified herein, amino acids in the variable regions are numbered using the Kabat numbering system and amino acids in the constant regions are numbered using the EU system.

[0073] As used herein, the term "monoclonal antibody" refers to an antibody produced by a single clone of B cells and binding to the same epitope. In contrast, the term "polyclonal antibody" refers to a population of antibodies produced by different B cells and binding to different epitopes of the same antigen. The term "antibody" includes, by way of example, monoclonal and polyclonal antibodies; chimeric and humanized antibodies; human or non-human antibodies; fully synthetic antibodies; and single-chain antibodies. Non-human antibodies can be humanized by recombinant methods to reduce their immunogenicity in humans.

[0074] The antibody can be an altered antibody (e.g., by mutation, deletion, substitution, conjugation to a non-antibody moiety). For example, the antibody can contain one or more variant amino acids (compared to naturally occurring antibodies) that change the properties (e.g., functional properties) of the antibody. Several such changes are known in the art that, for example, affect the half-life in a patient, effector functions, and / or immune response to the antibody. The term antibody also includes artificial polypeptide constructs that contain at least one antigen-binding site derived from an antibody.

[0075] An "antigen-binding fragment" of an antibody refers to one or more fragments or portions of an antibody that retain the ability to specifically bind to the antigen to which the whole antibody binds. It has been shown that the antigen-binding function of an antibody can be performed by fragments or portions of a full-length antibody. An antigen-binding fragment can contain the antigen-determining regions of an intact antibody (e.g., complementarity-determining regions (CDRs)). Examples of antigen-binding fragments of an antibody include Fab, Fab', F(ab') and F(ab') fragments. 2 Antigen-binding fragments of antibodies include, but are not limited to, Fv fragments, linear antibodies, and single chain antibodies. Antigen-binding fragments of antibodies can be derived from any animal species, such as rodents (e.g., mice, rats, or hamsters) and humans, or can be artificially generated.

[0076] Furthermore, although the two domains of the Fv fragment, VL and VH, are encoded by separate genes, the VL and VH can be joined by a synthetic linker that allows them to be produced using recombinant techniques as a single protein chain in which the VL and VH regions pair to form a monovalent molecule (known as a single-chain Fv (scFv)) (see, e.g., Bird et al. (1988) Science, 242:423-426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883). Such single-chain antibodies are also intended to be encompassed by the term "antigen-binding fragment" of an antibody.

[0077] Antigen-binding fragments are obtained using conventional techniques known to those of skill in the art, and the fragments are screened for utility in the same manner as intact antibodies. Antigen-binding fragments can be produced by recombinant DNA techniques or by enzymatic or chemical cleavage of intact immunoglobulins.

[0078] As used herein, the term "variable region" generally refers to a portion of an antibody, generally a light or heavy chain, typically about the amino-terminal 110-120 or 110-125 amino acids in a mature heavy chain and about 90-115 amino acids in a mature light chain, which vary widely in sequence between antibodies and are used in the binding and specificity of a particular antibody to a particular antigen. The sequence variability is concentrated in regions called complementarity determining regions (CDRs), while the more highly conserved regions within the variable domain are called framework regions (FRs). Without wishing to be bound by any particular mechanism or theory, it is believed that the CDRs of the light and heavy chains are primarily responsible for the interaction and specificity of the antibody with the antigen. In some embodiments, the variable region is a mammalian variable region, e.g., a human, mouse, or rabbit variable region. In some embodiments, the variable region comprises rodent or mouse CDRs and human framework regions (FRs). In some embodiments, the variable region is a primate (e.g., non-human primate) variable region. In some embodiments, the variable region comprises rodent or murine CDRs and primate (eg, non-human primate) FRs.

[0079] As used herein, the term "complementarity determining region" or "CDR" refers to each of the regions of an antibody variable domain that are hypervariable in sequence and / or form structurally defined loops (hypervariable loops) and / or contain antigen contact residues. An antibody can contain six CDRs, e.g., three in VH and three in VL.

[0080] The terms "VL," "VL region," and "VL domain" are used interchangeably herein to refer to a light chain variable region of an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof. In some aspects, a VL region is referred to herein as VL1 to denote a first light chain variable region, VL2 to denote a second light chain variable region, VL3 to denote a third light chain variable region, etc. A recited VL region (e.g., VL1) can have the same or different antigen-binding characteristics and / or the same or different sequence as another recited VL region (e.g., VL2).

[0081] The terms "VH," "VH region," and "VH domain" are used interchangeably herein to refer to a heavy chain variable region of an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody or antigen-binding fragment thereof. In some aspects, a VH region is referred to herein as VH1 to refer to a first heavy chain variable region, VH2 to refer to a second heavy chain variable region, VH3 to refer to a third heavy chain variable region, etc. A recited VH region (e.g., VH1) can have the same or different antigen binding characteristics and / or the same or different sequence as another recited VL region (e.g., VH2).

[0082] As used herein, "Kabat numbering" and similar terms are art-recognized and refer to a system for numbering amino acid residues in the variable regions of the heavy and light chains of an antibody or an antigen-binding fragment thereof. In some embodiments, CDRs can be determined according to the Kabat numbering system (see, for example, Kabat EA. & Wu TT (1971) Ann. NY Acad. Sci. 190: 382-391 and Kabat EA. et al., (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, USDepartment of Health and Human Services, NIH Publication, No. 91-3242). Using the Kabat numbering system, the CDRs in an antibody heavy chain molecule are typically located at amino acid positions 31-35 (which can optionally include one or two additional amino acids after 35, referred to as 35A and 35B in the Kabat numbering scheme) (CDR1), amino acid positions 50-65 (CDR2), and amino acid positions 95-102 (CDR3). Using the Kabat numbering system, the CDRs in an antibody light chain molecule are typically located at amino acid positions 24-34 (CDR1), amino acid positions 50-56 (CDR2), and amino acid positions 89-97 (CDR3).

[0083] As used herein, the terms "constant region" or "constant domain" are used interchangeably and refer to a portion of an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody or antigen-binding fragment thereof, e.g., the carboxyl-terminal portion of the light and / or heavy chain that is not directly involved in binding the antibody to the antigen but can exhibit various effector functions, such as interaction with the Fc region. Constant regions generally have a more conserved amino acid sequence than the variable region. In some embodiments, an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody or antigen-binding fragment thereof comprises a constant region or a portion thereof that is sufficient for antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC).

[0084] As used herein, the terms "fragment crystallizable region," "Fc region," or "Fc domain" are used interchangeably herein and refer to the tail region of an antibody that interacts with cell surface receptors called Fc receptors and some proteins of the complement system. The Fc region typically includes the CH2 and CH3 regions, and optionally includes the immunoglobulin hinge.

[0085] As used herein, the terms "immunoglobulin hinge", "hinge", "hinge domain" or "hinge region" are used interchangeably and refer to the section of an antigen-binding polypeptide, antigen-binding polypeptide complex, heavy chain between the Fab and Fc portions of an antibody or antigen-binding fragment thereof. The hinge provides structure, positioning, and flexibility that aid in the normal function of an antibody (e.g., to cross-link two antigens or to bind two antigenic determinants on the same antigen molecule). Immunoglobulin hinges are divided into upper, middle, and lower hinge regions that can be separated based on structural and / or genetic components. Immunoglobulin hinges of the present invention can contain one, two, or all three of these regions. Structurally, the upper hinge region extends from the C-terminus of CH1 to the first hinge disulfide bond. The middle hinge region extends from the first cysteine ​​to the last cysteine ​​in the hinge. The lower hinge region extends from the last cysteine ​​to the glycine of CH2. The cysteines present in the hinge form interchain disulfide bonds that link the immunoglobulin monomers.

[0086] As used herein, the term "Fab" refers to the region of an antibody that binds an antigen, which is usually composed of one constant domain and one variable domain of each of the heavy and light chains.

[0087] As used herein, the term "heavy chain" refers to a portion of an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody or antigen-binding fragment thereof, typically composed of a heavy chain variable region (VH), heavy chain constant region 1 (CH1), heavy chain constant region 2 (CH2), and heavy chain constant region 3 (CH3). A typical antibody is composed of two heavy chains and two light chains. When used in reference to an antibody, the heavy chain can refer to any of the different types based on the amino acid sequence of the constant region, e.g., alpha (α), delta (δ), epsilon (ε), gamma (γ), and mu (μ), giving rise to the IgA, IgD, IgE, IgG, and IgM classes of antibodies, including subclasses of IgG, such as IgG1, IgG2, IgG3, and IgG4, respectively. Heavy chain amino acid sequences are known in the art. In some embodiments, the heavy chain is a human heavy chain.

[0088] As used herein, the term "light chain" refers to a portion of an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody or antigen-binding fragment thereof, which is usually composed of a light chain variable region (VL) and a light chain constant region (CL). A typical antibody is composed of two light chains and two heavy chains. When used in reference to an antibody, the light chain can refer to any of the different types, e.g., kappa (κ) or lambda (λ), based on the amino acid sequence of the constant region. Light chain amino acid sequences are known in the art. In some embodiments, the light chain is a human light chain.

[0089] The term "chimeric" antibody or antigen-binding fragment thereof refers to an antibody or antigen-binding fragment thereof whose amino acid sequences are derived from more than one species. Typically, the variable regions of both the light and heavy chains correspond to the variable regions of an antibody or antigen-binding fragment thereof from one species of mammal (e.g., mouse, rat, rabbit, etc.) with the desired specificity, affinity, and function, while the constant regions are homologous to the sequences of an antibody or antigen-binding fragment thereof from another species (usually human) to avoid eliciting an immune response in that species.

[0090] The term "humanized" antibody or antigen-binding fragment thereof refers to a form of a non-human (e.g., murine) antibody or antigen-binding fragment that is a specific immunoglobulin chain, a chimeric immunoglobulin, or a fragment thereof that contains minimal non-human (e.g., murine) sequence. Typically, a humanized antibody or antigen-binding fragment thereof is a human immunoglobulin in which residues from its complementarity determining region (CDR) are replaced by residues from the CDR of a non-human species (e.g., mouse, rat, rabbit, hamster) having the desired specificity, affinity, and function (Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science 239:1534-1536 (1988)). In some embodiments, residues from the Fv framework region (FR) of a human immunoglobulin are replaced by the corresponding residues in an antibody or fragment from a non-human species having the desired specificity, affinity, and function. The humanized antibody or antigen-binding fragment thereof can be further modified by substitution of additional residues within the Fv framework regions and / or the replaced non-human residues to improve and optimize the specificity, affinity, and / or function of the antibody or antigen-binding fragment thereof. Generally, a humanized antibody or antigen-binding fragment thereof comprises substantially all of at least one, usually two or three, variable domains that contain all or substantially all of the CDR regions corresponding to a non-human immunoglobulin, while all or substantially all of the FR regions are of a human immunoglobulin consensus sequence. A humanized antibody or antigen-binding fragment thereof can also comprise at least a portion of a constant region that is typically of a human immunoglobulin. Examples of methods used to generate humanized antibodies are known and are described, for example, in U.S. Patent No. 5,225,539; Roguska et al., Proc. Natl. Acad. Sci., USA, 91(3):969-973 (1994), and Roguska et al., Protein Eng. 9(10):895-904 (1996).

[0091] As used herein, the term "human" antibody or antigen-binding fragment thereof means an antibody or antigen-binding fragment thereof having an amino acid sequence derived from the human immunoglobulin locus, and such an antibody or antigen-binding fragment thereof is produced using recombinant techniques known in the art. This definition of a human antibody or antigen-binding fragment thereof includes intact or full-length antibodies and fragments thereof.

[0092] An "isolated" polypeptide, polypeptide complex, antibody, antigen-binding fragment thereof, polynucleotide, vector, or host cell is a polypeptide, polypeptide complex, antibody, antigen-binding fragment thereof, polynucleotide, vector, or host cell that is in a form not found in nature. Isolated polypeptides, polypeptide complexes, antibodies, antigen-binding fragments thereof, polynucleotides, vectors, or host cells include those that have been purified to the extent that they are no longer in a form in which they are found in nature. In some embodiments, an isolated polypeptide, polypeptide complex, antibody, antigen-binding fragment thereof, polynucleotide, vector, or host cell is substantially pure. As used herein, "substantially pure" refers to a material that is at least 50% pure (i.e., free from contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 99% pure.

[0093] The terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymers can be linear or branched, can contain modified amino acids, and can be interrupted by non-amino acids. The terms also include amino acid polymers that have been modified, naturally or by intervention, for example, by disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides that contain one or more analogs of an amino acid (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art. Because the polypeptides of the present invention are based on antibodies, it is understood that in some aspects the polypeptides can occur as single chains or linked chains.

[0094] The use of the alternative (e.g., "or") should be understood to mean either one, both, or any combination of the alternatives. As used herein, the indefinite article "a" or "an" should be understood to refer to "one or more" of any cited or listed components.

[0095] As used herein, the term "and / or" should be interpreted as a specific disclosure of each of the two specified features or components, with or without the other. Thus, the term "and / or" used herein in phrases such as "A and / or B" is intended to include "A and B," "A or B," "A" (single), and "B" (single). Similarly, the term "and / or" used in phrases such as "A, B, and / or C" is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (single); B (single); and C (single).

[0096] As used herein, where an embodiment is described using phrases such as "including," "having," etc., it is understood that other similar embodiments described using the terms "consisting of" and / or "consisting essentially of" are also provided.

[0097] As used herein, the term "about" refers to a value or composition that is within an acceptable error range for a particular value or composition as determined by one of ordinary skill in the art, which will depend in part on how the value or composition is measured or determined, i.e., the limitations of the measurement system. For example, "about" can mean within 1 or more than 1 standard deviation, as is customary in the art. Alternatively, "about" can mean within a range of up to 10% or 20% (i.e., ±10% or ±20%). For example, about 3 mg includes any number between 2.7 mg and 3.3 mg (for 10%), or between 2.4 mg and 3.6 mg (for 20%). Furthermore, particularly with respect to biological systems or processes, the term can mean up to an order of magnitude, or up to 5 times the value. Unless otherwise indicated, when a particular value or composition is provided in this application and claims, the meaning of "about" should be assumed to be within an acceptable error range for that particular value or composition.

[0098] As described herein, any numerical range, concentration range, percentage range, ratio range, or integer range, unless otherwise indicated, is understood to include any integer value within the recited range, and, where appropriate, fractions thereof (such as 1 / 10 and 1 / 100 of an integer).

[0099] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. For example, the Concise Dictionary of Biomedicine and Molecular Biology, Juo, Pei-Show, 2nd ed., 2002, CRC Press; The Dictionary of Cell and Molecular Biology, 5th ed., 2013, Academic Press; and the Oxford Dictionary Of Biochemistry And Molecular Biology, 2006, Oxford University Press provide those of ordinary skill in the art with a general dictionary of many of the terms used in this disclosure.

[0100] Units, prefixes, and symbols are indicated in the format accepted by the Systeme International de Unites (SI). Numerical ranges are intended to be inclusive of the numbers defining the range. The headings provided herein are not intended to be limiting of the various aspects of the disclosure, which may be found by reference to the specification in its entirety. Thus, terms defined herein are more fully defined by reference to the specification in its entirety.

[0101] Various aspects are described in further detail in the following sections.

[0102] Antigen-binding polypeptides and antigen-binding polypeptide complexes In some aspects, the present invention is directed to antigen-binding polypeptides and antigen-binding polypeptide complexes that have particular structural features.

[0103] Bispecific constructs In some embodiments, the present invention is directed to antigen-binding polypeptides and antigen-binding polypeptide complexes having a structure represented by VL1-VL2-VH2-VH1 or VH1-VH2-VL2-VL1. In some embodiments, the antigen-binding polypeptide or antigen-binding polypeptide complex contains an amino acid linker between any two regions depicted in the structures described herein. In some embodiments, the antigen-binding polypeptide or antigen-binding polypeptide complex can contain one or more Fc regions, CH1 regions, or CL regions, or any combination thereof. In some embodiments, the antigen-binding polypeptide complex is an antibody or an antigen-binding fragment thereof.

[0104] The antigen-binding polypeptides and antigen-binding polypeptide complexes described herein specifically bind to HIV proteins. This includes specific binding to one or more HIV proteins and specific binding to one or more epitopes on the same HIV protein. In some embodiments, the HIV protein is selected from the group consisting of an HIV envelope protein, an HIV structural protein, an HIV functional protein, or an HIV accessory protein. In some embodiments, the HIV envelope protein is an HIV envelope glycoprotein (Env), an HIV envelope glycoprotein gp160, an HIV envelope surface glycoprotein gp120, or an HIV transmembrane envelope protein gp41. In some embodiments, the HIV structural protein is p17, p24, p7, or p55. In some embodiments, the HIV functional protein is p66, HIV-1 protease (PR), or p31. In some embodiments, the HIV accessory protein is Nef, Tat, Rev, Vif, Vpr, or Vpu.

[0105] In some embodiments, an antigen-binding polypeptide of the invention has a structure represented by VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; or VH1-L1-VH2-L2-VL2-L3-VL1, where VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, and L3 are amino acid linkers.

[0106] In some embodiments, an antigen-binding polypeptide complex of the invention comprises a first polypeptide and a second polypeptide; the first polypeptide has a structure represented by VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; or VH1-L1-VH2-L2-VL2-L3-VL1; the second polypeptide has a structure represented by VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; or or VH1-L1-VH2-L2-VL2-L3-VL1; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, and L3 are amino acid linkers.

[0107] In some embodiments, an antigen-binding polypeptide of the invention has a structure represented by VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; wherein VL1 is a first immunoglobulin that specifically binds to an HIV protein. VL1 is a light chain variable region; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, and L4 are amino acid linkers.

[0108] In some embodiments, an antigen-binding polypeptide complex of the invention comprises a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; VL1-L1-VH2-L2-VL2-L3-VL1-Fc; VH2-L3-VH1-L4-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; the second polypeptide is Fc; VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc ; VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising an immunoglobulin heavy chain constant region 2 (CH2), an immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, and L4 are amino acid linkers.

[0109] In some embodiments, the antigen-binding polypeptides of the invention are VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL; VL1-L1-VL2-L2-VH2-L3-VL1-L4-CH1-L5-CL; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1; or VH1-L1-VH2-L2-VL2-L3-VL1-L4 -CL-L5-CH1; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, and L5 are amino acid linkers.

[0110] In some embodiments, an antigen-binding polypeptide complex of the invention comprises a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-CH1; VH1-VH2-VL2-VL1-CH1; VL1-VL2-VH2-VH1-CL; VH1-VH2-VL2-VL1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CH1-CL; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1; VL1-L1-VL 2-L2-VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1-L 1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1- L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL; H2-L2-VL2-L3-VL1-L4-CL-L5-CH1; the second polypeptide has a structure represented by VL1-VL2-VH2-VH1-CH1; VL1-VL2-VH2-VH1-CH1; VH1-VH2-VL2-VL1-CH1; VL1-VL2-VH2-VH1-CL; VH1-VH2-VL2-VL1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1 1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L 4-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1 -L4-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1;or has a structure represented by VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an IV protein; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, and L5 are amino acid linkers;

[0111] In some embodiments, the antigen-binding polypeptides of the invention comprise VL1-VL2-VH2-VH1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-CH1-Fc; VH1-VH2-VL2-VL1-CL-CH1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc; CH1-L5-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-Fc;VL1- L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L6-Fc;VL1-L1-VL2-L2-V H2-L3-VH1-L4-CL-L5-CH1-L6-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; and VH1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein. VH1 is an immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; Fc is a region containing immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0112] In some embodiments, an antigen-binding polypeptide complex of the invention comprises a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-CH1-Fc; VH1-VH2-VL2-VL1-CH1-Fc; VL1-VL2-VH2-VH1-CL-Fc; VH1-VH2-VL2-VL1-CL-Fc; VL1-VL2-VH2-VH1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-CH1-Fc; VH1-VH2-VL2-VL1 -CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;VH1-L1-VH2-L2-V L2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1- VH2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5 -CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL1-L1-VL2-L2- VH2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5- CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL 2-L3-VL1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc;VH 1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4 -CH1-L5-CL-L6-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L6-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc; the second polypeptide has a structure represented by Fc; VL1-VL2-VH2-VH1-CH1-Fc; VH1-VH2-VL2-VL1-CH1-Fc; VL1-VL2-VH2-VH1-CL-Fc;VH1-VH2-VL2-VL1-CL-Fc;VL1-VL2-VH2-VH1-CH1-CL-Fc;VH1-VH2-VL2-VL1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CL-CH1-Fc;VH1-VH2-VL2-VL1-CL-CH1 -Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-V L1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1-VH2-L2- VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL1-L1-VL2-L2-VH2-L3 -VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-Fc ;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL2-L3-V L1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc;VH1-L1-V H2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1- VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L6-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; 3-VL1-L4-CL-L5-CH1-L6-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is an immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region;Fc is a region containing immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, and L6 are amino acid linkers;

[0113] In some embodiments, the antigen-binding polypeptide complex of the present invention includes polypeptide 1 and polypeptide 2; polypeptide 1 is VL1-VL2-VH2-VH1; -L1-VH2-L2-VL2-L3-VL1;VL1-VL2-VH2-VH1-Fc;VH1-VH2-VL2-VL1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-Fc;VL1-L1 -VL2-L2-VH2-L3-VH1-L4-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc;VL1-VL2-VH2-VH1-CH1;VH1-VH2-VL2-VL1-CH1;VL1-VL2-VH2-VH1-CL;VH1-VH2 -VL2-VL1-CL;VL1-VL2-VH2-VH1-CH1-CL;VH1-VH2-VL2-VL1-CH1-CL;VL1-VL2-VH2-VH1-CL-CH1;VH1-VH2-VL2-VL1-CL-CH1;VL1-L1-VL2-L2-VH2- L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1-L1-VL2-L2- VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1;VH1-L1-VH2-L2-VL2-L3-V L1-L4-CL-L5-CH1;VL1-VL2-VH2-VH1-CH1-Fc;VH1-VH2-VL2-VL1-CH1-Fc;VL1-VL2-VH2-VH1-CL-Fc;VH1-VH2-VL2-VL1-CL-Fc;VL1-VL2-VH2-VH1- CH1-CL-Fc;VH1-VH2-VL2-VL1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CL-CH1-Fc;VH1-VH2-VL2-VL1-CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L6-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; or has a structure represented by VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc; The second polypeptide is VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; VH1-L1-VH2-L2-VL2-L3-VL1; VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; VL1-VL2-VH2-VH1-CH1; VH1-VH2-VL2-VL1-CH1; VL1-VL2-VH2-VH1-CL; VH1-VH2-VL2-VL1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL;<h2 style=";text-align:left;direction:ltr">VL1-VL2-VH2-VH1-CL-CH1;VH1-VH2-VL2-VL1-CL-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1- L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1;VL1-VL2-VH2-VH1-CH1-Fc;VH1-VH2-VL2-VL1-CH1-Fc;VL1-VL2-VH2-VH1-CL-Fc;VH1-VH2-VL2-VL1-CL-Fc;VL1-VL2-VH2-VH1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CL-Fc CH1-Fc;VH1-VH2-VL2-VL1-CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH 1-L5-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VL1-L4-CL-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L6-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein. VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0114] In other aspects, the invention is directed to antigen-binding polypeptides or antigen-binding polypeptide complexes comprising a polypeptide having a structure represented by VL1-VL2-VH2-VH1 or VH1-VH2-VL2-VL1 having two Fc regions. In some aspects, the antigen-binding polypeptide or antigen-binding polypeptide complex is VL1-VL2-VH2-VH1-Fc-Fc; VH1-VH2-VL2-VL1-Fc-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc-Fc ;VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc-Fc;VL1 -L1-VL2-L2-VH2-L3-VH1-L4-Fc-L5-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc-L5-F c), wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, and L5 are amino acid linkers.

[0115] In other aspects, the invention is directed to antigen-binding polypeptides or antigen-binding polypeptide complexes comprising a polypeptide having a structure represented by VL1-VL2-VH2-VH1 or VH1-VH2-VL2-VL1 having one or two CH3 regions. In some aspects, the antigen-binding polypeptide or antigen-binding polypeptide complex is VL1-VL2-VH2-VH1-CH3; VH1-VH2-VL2-VL1-CH3; VL1-L1-VL2-L2-VH2-L3-VH1-CH3; VH1-L1-VH2-L2-VL2-L3-VL1-CH3; VL1-L1-VH2-L2-VL2-L3-VL1-CH3; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH3; VH1-L1-VH 2-L2-VL2-L3-VL1-L4-CH3;VL1-VL2-VH2-VH1-CH3-CH3;VH1-VH2-VL2-VL1-CH3-CH3;VL1-L1-VL2-L2-VH2 -L3-VH1-CH3-CH3;VH1-L1-VH2-L2-VL2-L3-VL1-CH3-CH3;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH3-CH3;VH1- VL1-VH2-L2-VL2-L3-VL1-L4-CH3-CH3; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH3-L5-CH3; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH3-L5-CH3; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH3 is an immunoglobulin heavy chain constant region 3; and L1, L2, L3, L4, and L5 are amino acid linkers.

[0116] In some embodiments of the antigen-binding polypeptides or antigen-binding polypeptide complexes of the invention, VH1 and VH2 each comprise a heavy chain variable region derived from a PGT121 antibody, a VRC01 antibody, a 10E8v4 antibody, or a PG16 antibody, or a variant thereof. In some embodiments, VL1 and VL2 each comprise a light chain variable region derived from a PGT121 antibody, a VRC01 antibody, a 10E8v4 antibody, or a PG16 antibody, or a variant thereof. In some embodiments, VH1 and VH2 each comprise a heavy chain variable region derived from a PGT121 antibody, a VRC01 antibody, a 10E8v4 antibody, or a PG16 antibody, or a variant thereof, and VL1 and VL2 each comprise a light chain variable region derived from a PGT121 antibody, a VRC01 antibody, a 10E8v4 antibody, or a PG16 antibody, or a variant thereof.

[0117] In some embodiments, the antigen-binding polypeptide or antigen-binding polypeptide complex comprises VH and VL sequences derived from broadly neutralizing antibodies targeting CD4bs, including VRC01, VRC03, 3BNC117, N6, N49P7, 3BNC60, VRC-PG04, VRC-PG20, NIH45-46, VRC-CH31, 12A12, CH103, 8ANC131, VRC13, and VRC16.

[0118] In some embodiments, VH1 and VH2 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 20-23. In some embodiments, VL1 and VL2 each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 24-27. In some embodiments, VH1 and VH2 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 20-23, and VL1 and VL2 each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 24-27.

[0119] In some embodiments, the VH1 and VH2 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention each comprise a CDR1 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 60, 63, 66, and 69; a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 61, 64, 67, and 70; and a CDR3 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 62, 65, 68, and 71. and / or VL1 and VL2 each comprise a CDR1 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 72, 75, 78, and 81; a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 73, 76, 79, and 82; and a CDR3 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 74, 77, 80, and 83.

[0120] Trispecific constructs In some embodiments, the present invention is directed to an antigen-binding polypeptide complex (e.g., an antibody or antigen-binding fragment thereof) comprising a first polypeptide having a structure represented by VL1-VL2-VH2-VH1 or VH1-VH2-VL2-VL1, and a second polypeptide having a structure represented by VL3-VH3 or VH3-VL3. In some embodiments, the present invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide having a structure represented by VL1-VL2-VH2-VH1 or VH1-VH2-VL2-VL1; a second polypeptide having a structure represented by VL3; and a third polypeptide having a structure represented by VH3. In some embodiments, the antigen-binding polypeptide complex contains an amino acid linker between any two regions depicted in the structures described herein. In some embodiments, the antigen-binding polypeptide complex contains an Fc region, a CH1 region, a CL region, or any combination thereof. In some embodiments, the antigen-binding polypeptide complex is an antibody or antigen-binding fragment thereof.

[0121] The antigen-binding polypeptides and antigen-binding polypeptide complexes described herein specifically bind to HIV proteins. This includes specific binding to one or more HIV proteins and specific binding to one or more epitopes on the same HIV protein. In some embodiments, the HIV protein is selected from the group consisting of an HIV envelope protein, an HIV structural protein, an HIV functional protein, or an HIV accessory protein. In some embodiments, the HIV envelope protein is an HIV envelope glycoprotein (Env), an HIV envelope glycoprotein gp160, an HIV envelope surface glycoprotein gp120, or an HIV transmembrane envelope protein gp41. In some embodiments, the HIV structural protein is p17, p24, p7, or p55. In some embodiments, the HIV functional protein is p66, HIV-1 protease (PR), or p31. In some embodiments, the HIV accessory protein is Nef, Tat, Rev, Vif, Vpr, or Vpu.

[0122] In some embodiments, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide has a structure represented by VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; or VH1-L1-VH2-L2-VL2-L3-VL1; the second polypeptide has a structure represented by VL3-VH3; VH3-VL3; VL3-L4-VH3; or VH3-L4-VL3; and VL1 is a first polypeptide that specifically binds to an HIV protein. VL1 is an immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, L3, and L4 are amino acid linkers.

[0123] In another aspect, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VL1-Fc; H2-L3-VH1-L4-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; the second polypeptide has a structure represented by VL3-VH3-Fc; VH3-VL3-Fc; VL3-L5-VH3-Fc; VH3-L5-VL3-Fc; VL3-L5-VH3-L6-Fc; or VH3-L5-VL3-L6-Fc; L1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0124] In another aspect, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-CH1; VH1-VH2-VL2-VL1-CH1; VL1-VL2-VH2-VH1-CL; VH1-VH2-VL2-VL1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1; VL1-L1-VL2-L2-VH2 -L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1-L1-VL2-L2-V H2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1-L1-VL2-L2-VH 2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL;VL 1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1; or VH1-L1-VH2-L2-VL2-L3-VL1 -L4-CL-L5-CH1; the second polypeptide has a structure represented by VL3-VH3-CH1; VH3-VL3-CH1; VL3-VH3-CL; VH3-VL3-CL; VL3-VH3-CH1-CL; VH3-VL3-CH1-CL; VL3-VH3-CL-CH1; VH3-VL3-CL-CH1; VL3-CL-VH3-CH1; VL3-CH1-VH3-CL; VH3-CH1-VL3-CL; VH3-CL-VL3-CH1; VL3-L6-VH3-L7-CH1; VH3-L6-VL3-L7-CH1; VL3-L6-VH3- L7-CL;VH3-L6-VL3-L7-CL;VL3-L6-VH3-L7-CH1-L8-CL;VH3-L6-VL3-L7-CH1-L8-CL;VL3-L6-VH3-L7-CL-L8-CH1;VH3-L6-VL3-L7-CL-L8-CH1;VL3-L6 -CL-L7-VH3-L8-CH1;VL3-L6-CH1-L7-VH3-L8-CL;VH3-L6-CH1-L7-VL3-L8-CL;VH3-L6-CL-L7-VL3-L8-CH1;VL3-VH3-L6-CH1-CL;VH3-VL3-L6-CH1-CL;VL3-VH3-L6-CL-CH1; VH3-VL3-L6-CL-CH1; VL3-CL-L6-VH3-CH1; VL3-CH1-L6-VH3-CL; VH3-CH1-L6-VL3-CL; or VH3-CL-L6-VL3-CH1; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL3 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein. VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, and L8 are amino acid linkers.

[0125] In another aspect, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-CH1-Fc; VH1-VH2-VL2-VL1-CH1-Fc; VL1-VL2-VH2-VH1-CL-Fc; VH1-VH2-VL2-VL1-CL-Fc; VL1-VL2-VH2-VH1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-CH1-Fc; VH1-VH2-VL2-VL1 -CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;VH1-L1-VH2-L2-V L2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1-V H2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-C L-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL1-L1-VL2-L2-VH 2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH 1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL2-L 3-VL1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc;VH1-L1 -VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1 -L5-CL-L6-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L6-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc; the second polypeptide has a structure represented by VL3-VH3-CH1-Fc; VH3-VL3-CH1-Fc; VL3-VH3-CL-Fc; VH3-VL3-CL-Fc; VL3-VH3-CH1-CL-Fc;VH3-VL3-CH1-CL-Fc;VL3-VH3-CL-CH1-Fc;VH3-VL3-CL-CH1-Fc;VL3-CL-VH3-CH1-Fc;VL3-CH1-VH3-CL-Fc;VH3-CH1-VL3-CL-Fc;VH3-CL-VL3-CH1 -Fc;VL3-L7-VH3-L8-CH1-Fc;VH3-L7-VL3-L8-CH1-Fc;VL3-L7-VH3-L8-C L-Fc;VH3-L7-VL3-L8-CL-Fc;VL3-L7-VH3-L8-CH1-L9-CL-Fc;VH3-L7-VL3 -L8-CH1-L9-CL-Fc;VL3-L7-VH3-L8-CL-L9-CH1-Fc;VH3-L7-VL3-L8-CL-L9-CH1-Fc;VL3-L7-CL-L8-VH3-L9-CH1-Fc;VL3-L7-CH1-L8-VH3-L9-CL- Fc;VH3-L7-CH1-L8-VL3-L9-CL-Fc;VH3-L7-CL-L8-VL3-L9-CH1-Fc;VL3-L7-VH3-L8-CH1-L9-CL-L10-Fc;VH3-L7-VL3-L8-CH1-L9-CL-L10-Fc;VL3- L7-VH3-L8-CL-L9-CH1-L10-Fc;VH3-L7-VL3-L8-CL-L9-CH1-L10-Fc;VL3-L7-CL-L8-VH3-L9-CH1-L10-Fc;VL3-L7-CH1-L8-VH3-L9-CL-L10-Fc;VH 3-L7-CH1-L8-VL3-L9-CL-L10-Fc;VH3-L7-CL-L8-VL3-L9-CH1-L10-Fc;VL3-VH3-L7-CH1-CL-Fc;VH3-VL3-L7-CH1-CL-Fc;VL3-VH3-L7-CL-CH1-Fc; VH3-VL3-L7-CL-CH1-Fc; VL3-CL-L7-VH3-CH1-Fc; VL3-CH1-L7-VH3-CL-Fc; VH3-CH1-L7-VL3-CL-Fc; or VH3-CL-L7-VL3-CH1-Fc; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein;VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region that includes immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge, where CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, and L10 are amino acid linkers;

[0126] In another aspect, the present invention is directed to an antigen-binding polypeptide complex containing the 1st polypeptide and the 2nd polypeptide; the 1st polypeptide is VL1-VL2-VH2-VH1; 1-L1-VH2-L2-VL2-L3-VL1;VL1-VL2-VH2-VH1-Fc;VH1-VH2-VL2-VL1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-Fc;VL1-L 1-VL2-L2-VH2-L3-VH1-L4-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc;VL1-VL2-VH2-VH1-CH1;VH1-VH2-VL2-VL1-CH1;VL1-VL2-VH2-VH1-CL;VH1-VH 2-VL2-VL1-CL;VL1-VL2-VH2-VH1-CH1-CL;VH1-VH2-VL2-VL1-CH1-CL;VL1-VL2-VH2-VH1-CL-CH1;VH1-VH2-VL2-VL1-CL-CH1;VL1-L1-VL2-L2-VH2- L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1-L1-VL2-L2- VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1;VH1-L1-VH2-L2-VL2-L3-V L1-L4-CL-L5-CH1;VL1-VL2-VH2-VH1-CH1-Fc;VH1-VH2-VL2-VL1-CH1-Fc;VL1-VL2-VH2-VH1-CL-Fc;VH1-VH2-VL2-VL1-CL-Fc;VL1-VL2-VH2-VH1- CH1-CL-Fc;VH1-VH2-VL2-VL1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CL-CH1-Fc;VH1-VH2-VL2-VL1-CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;<h2 style=";text-align:left;direction:ltr">VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3- VL1-L4-CL-L5-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5 -CL-L6-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc;またはVH1-L 1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc VL3-VH3;VH3-VL3;VL3-L4-VH3;VH3-L4-VL3;VL3-VH3-Fc;VH3-VL3-Fc;VL 3-L4-VH3-Fc;VH3-L4-VL3-Fc;VL3-VH3-CH1;VH3-VL3-CH1;VL3-VH3-CL;V H3-VL3-CL;VL3-VH3-CH1-CL;VH3-VL3-CH1-CL;VL3-VH3-CL-CH1;VH3-VL3-CL-CH1;VL3-CL-VH3-CH1;VL3-CH1-VH3-CL;VH3-CH1-VL3-CL;VH3-CL-VL3-CH1;VL3-L7-VH3-L8-CH1;VH3-L7-VL3-L8-CH1;VL3-L7-VH3-L8-CL;VH3-L7-VL3-L8-CL;VL3-L7-VH3-L8-CH1-L9-CL;VH3-L7-VL3-L8-CH1-L9-CL;<h2 style=";text-align:left;direction:ltr">VL3-L7-VH3-L8-CL-L9-CH1;VH3-L7-VL3-L8-CL-L9-CH1;VL3-L7-CL-L8-VH3-L9-CH1;VL3-L7-CH1-L8-VH3-L9-CL;VH3-L7-CH1-L8-VL3-L9-CL;VH3-L7-CL-L8-VL3-L9-CH1;VL3-VH3-L7-CH1-CL;VH3-VL3-L7-CH1-CL;VL3-VH3-L7-CL-CH1;VH3-VL3-L7-CL-CH1;VL3-CL-L7-VH3-CH1;VL3-CH1-L 7-VH3-CL;VH3-CH1-L7-VL3-CL;VH3-CL-L7-VL3-CH1;VL3-VH3-CH1-Fc;VH3-VL3-CH1-Fc;VL3-VH3-CL-Fc;VH3-VL3-CL-Fc;VL3-VH3-CH1-CL-Fc;V H3-VL3-CH1-CL-Fc;VL3-VH3-CL-CH1-Fc;VH3-VL3-CL-CH1-Fc;VL3-CL-VH3-CH1-Fc;VL3-CH1-VH3-CL-Fc;VH3-CH1-VL3-CL-Fc;VH3-CL-VL3-CH1- Fc;VL3-L7-VH3-L8-CH1-Fc;VH3-L7-VL3-L8-CH1-Fc;VL3-L7-VH3-L8-CL-Fc;VH3-L7-VL3-L8-CL-Fc;VL3-L7-VH3-L8-CH1-L9-CL-Fc;VH3-L7-VL3-L8-CH1-L9-CL-Fc;VL3-L7-VH3-L8-CL-L9-CH1-Fc;VH3-L7-VL3-L8-CL-L9-CH1-Fc;VL3-L7-VL3-L8-CL-L9-CH1-Fc;VL3-L7-VL3-L8-CL-L9-CH1-Fc;VL3-L7-CL-L8-VH3-L9-CH1-Fc;VL3-L7-CH1-L8-VH3-L9-CL- Fc;VH3-L7-CH1-L8-VL3-L9-CL-Fc;VH3-L7-CL-L8-VL3-L9-CH1-Fc;VL3-L7-VH3-L8-CH1-L9-Fc;VH3-L7-VL3-L8-CH1-L9-Fc;VL3-L7-VH3-L8-CL-L9-Fc;VH3-L7-VL3-L8-CL-L9-Fc;VL3-L7-VH3-L8-CH1-L9-CL-L10-Fc;VH3-L7-VL3-L8-CH1-L9-CL-L10-Fc;VL3-L7-VH3-L8-CL-L9-CH1-L10-Fc;VH3-L7-VL3-L8-CL-L9-CH1-L10-Fc;VL3-L7-CL-L8-VH3-L9-CH1-L10-Fc;VL3-L7-CH1-L8-VH3-L9-CL-L10-Fc ;VH3-L7-CH1-L8-VL3-L9-CL-L10-Fc;VH3-L7-CL-L8-VL3-L9-CH1-L10-Fc;VL3-VH3-L7-CH1-CL-Fc;VH3-VL3-L VH3-VH3-L7-CL-CH1-Fc; VH3-VL3-L7-CL-CH1-Fc; VL3-CL-L7-VH3-CH1-Fc; VL3-CH1-L7-VH3-CL-Fc; VH3-CH1-L7-VL3-CL-Fc; or VH3-CL-L7-VL3-CH1-Fc; wherein VL1 is a first immunoglobulin light chain that specifically binds to an HIV protein. VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, and L10 are amino acid linkers.

[0127] In another aspect, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide has a structure represented by VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; or VH1-L1-VH2-L2-VL2-L3-VL1; the second polypeptide has a structure represented by VL3; the third polypeptide has a structure represented by VH3; and VL1 is a first polypeptide that specifically binds to an HIV protein. VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, and L3 are amino acid linkers.

[0128] In another aspect, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; or VH1-L1-VH2-L2-VL2-L3-VH1-L4-Fc; the second polypeptide has a structure represented by VL3; or VL3-L5; the third polypeptide has a structure represented by VH3-Fc; or VH3-L6-Fc; and VL1 is an HIV protein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0129] In another aspect, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; L1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; the second polypeptide has a structure represented by VL3-Fc; or VL3-L5-Fc; the third polypeptide has a structure represented by VH3; or VH3-L6; and VL1 is an HIV protein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0130] In another aspect, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-CH1; VH1-VH2-VL2-VL1-CH1; VL1-VL2-VH2-VH1-CL; VH1-VH2-VL2-VL1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1; VL1 -L1-VL2-L2-VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL; the second polypeptide has a structure represented by VL3-CH1; VL3-CL; VL3-L6-CH1; or VL3-L6-CL; the third polypeptide has a structure represented by VH3-CH1; VH3-CL; VH3-L7-CH1; or VH3-L7-CL; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein. VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers.

[0131] In another aspect, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide is VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; VH1-L1-VH2-L2-VL2-L3-VL1; VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1- Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4 -Fc;VL1-VL2-VH2-VH1-CH1;VH1-VH2-VL2-VL1-CH1;VL1-VL2-VH2-VH1-CL ;VH1-VH2-VL2-VL1-CL;VL1-VL2-VH2-VH1-CH1-CL;VH1-VH2-VL2-VL1-CH1-CL;VL1-VL2-VH2-VH1-CL-CH1;VH1-VH2-VL2-VL1-CL-CH1;VL1-L1-VL2-L 2-VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1-L1-VL 2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1-L1-VL 2-L2-VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L 5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1;VH1-L1-VH2-L2-VL2-L 3-VL1-L4-CL-L5-CH1;VL1-VL2-VH2-VH1-CH1-Fc;VH1-VH2-VL2-VL1-CH1- Fc;VL1-VL2-VH2-VH1-CL-Fc;VH1-VH2-VL2-VL1-CL-Fc;VL1-VL2-VH2-VH1 -CH1-CL-Fc;VH1-VH2-VL2-VL1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CL-CH1-Fc;VH1-VH2-VL2-VL1-CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3- VH1-L4-CH1-L5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-V L1-L4-CL-L5-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-C L-L5-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-C L-L6-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc has the structure shown by; 3;VL3-Fc;VL3-CH1;VL3-CL;VL3-CH1-CL;VL3-CL-CH1;VL3-CH1-Fc;VL3-CL-Fc;VL3-CH1-CL-Fc;VL3-CL-CH1-Fc;VL3-L7-Fc;VL3-L7-CH1;VL3-L7-CL ;VL3-L7-CH1-L8-CL;VL3-L7-CL-L8-CH1;VL3-L7-CH1-L8-Fc;VL3-L7-CL-L8-Fc;VL3-L7-CH1-L8-CL-Fc;VL3-L7-CL-L8-CH1-Fc;VL3-L7-CH1-L8-CL -L9-Fc; or VL3-L7-CL-L8-CH1-L9-Fc by VL3-L7-CL-L8-CH1-L9-Fc;VH3-CH1-CL-Fc;VH3-CL-CH1-Fc;VH3-L10-Fc;VH3-L10-CH1;VH3-L10-CL;VH3-L10-CH1-L11-CL;V H3-L10-CL-L11-CH1;VH3-L10-CH1-L11-Fc;VH3-L10-CL-L11-Fc;VH3-L10-CH1-L11-CL-Fc;VH3-L1 VH3-L10-CH1-L11-CL-L12-Fc; or VH3-L10-CL-L11-CH1-L12-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein. VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, and L12 are amino acid linkers.

[0132] In some embodiments, the present invention provides a method for the preparation of a fusion protein comprising administering to a subject an endonuclease an antibody or endonuclease an antibody comprising the fusion protein of the present invention, the fusion protein of the present invention being selected from the group consisting of VL1-VL2-VH2-VH1-Fc, VH1-VH2-VL2-VL1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-Fc, VH1-L1-VH2-L2-VL2-L3-VH1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc, or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc. and a second polypeptide having a structure represented by VL3-VH3-Fc, VL3-L5-VH3-Fc, VH3-VL3-Fc, VH3-L5-VL3-Fc, VL3-L5-VH3-L6-Fc, or VH3-L5-VL3-L6-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0133] In some embodiments, the invention provides a method for the preparation of a polypeptide comprising a first polypeptide having a structure represented by VL1-VL2-VH2-VH1-Fc, VH1-VH2-VL2-VL1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-Fc, VH1-L1-VH2-L2-VL2-L3-VH1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc, or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; and a third polypeptide having a structure represented by VL3-CL, VL3-L7-CL, VH3-CL, or VH3-L7-CL. VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers.

[0134] In some embodiments, the invention provides a method for the preparation of a polypeptide comprising a first polypeptide having a structure represented by VL1-VL2-VH2-VH1-Fc, VH1-VH2-VL2-VL1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-Fc, VH1-L1-VH2-L2-VL2-L3-VH1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; and a polypeptide comprising a first polypeptide having a structure represented by CL-VL3-VH3-CH1-Fc, CL-L5-VL3-L6-VH3-L7-CH1- Fc, CL-L5-VL3-L6-VH3-L7-CH1-L8-Fc, CL-VH3-VL3-CH1-Fc; CL-L5-VH3-L6-VL3-L7-CH1-Fc, CL-L5-VH3-L6-VL3-L7-CH1-L8-Fc, CH1-VL3-VH3- CL-Fc, CH1-L5-VL3-L6-VH3-L7-CL-Fc, CH1-L5-VL3-L6-VH3-L7-CL-L8-Fc, CH1-VH3-VL3-CL-Fc; CH1-L5-VH3-L6-VL3-L7-CL-Fc, or CH1-L5-VH The present invention is directed to an antigen-binding polypeptide complex (e.g., an antibody or antigen-binding fragment thereof) comprising a second polypeptide having a structure represented by: 3-L6-VL3-L7-CL-L8-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; and VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein. VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, and L8 are amino acid linkers.

[0135] In some embodiments, the invention provides a method for the preparation of a polypeptide comprising a first polypeptide having a structure represented by VL1-VL2-VH2-VH1-Fc, VH1-VH2-VL2-VL1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-Fc, VH1-L1-VH2-L2-VL2-L3-VH1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc, or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc; and a second polypeptide having a structure represented by VL3-CL-VH3-CH1-Fc, VL3-L5-CL-L6-VH3-L7-CH1- Fc, VL3-L5-CL-L6-VH3-L7-CH1-L8-Fc, VH3-CL-VL3-CH1-Fc, VH3-L5-CL-L6-VL3-L7-CH1-Fc, VH3-L5-CL-L6-VL3-L7-CH1-L8-Fc, VL3-CH1-VH3- CL-Fc, VL3-L5-CH1-L6-VH3-L7-CL-Fc, VL3-L5-CH1-L6-VH3-L7-CL-L8-Fc, VH3-CH1-VL3-CL-Fc, VH3-L5-CH1-L6-VL3-L7-CL-Fc, or VH3-L5-CH and a second polypeptide having a structure represented by the formula: VL1-L6-VL3-L7-CL-L8-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; and VH1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein. VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, and L8 are amino acid linkers.

[0136] In some embodiments, the invention provides a method for the preparation of a polypeptide comprising a first polypeptide having a structure represented by VL1-VL2-VH2-VH1-Fc, VH1-VH2-VL2-VL1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-Fc, VH1-L1-VH2-L2-VL2-L3-VH1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc, or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc, and a second polypeptide having a structure represented by VL3-VH3-CL-CH1-Fc, VL3-L5-VH3-L6 ... 3-L6-CL-L7-CH1-Fc, VL3-L5-VH3-L6-CL-L7-CH1-L8-Fc, VH3-VL3-CL-CH1-Fc, VH3-L5-VL3-L6-CL-CH1-Fc, VH3-L5-VL3-L6-CL-L7-CH1-Fc, VH3-L5- VL3-L6-CL-L7-CH1-L8-Fc, VL3-VH3-CH1-CL-Fc, VL3-L5-VH3-L6-CH1-CL-Fc, VL3-L5-VH3-L6-CH1-L7-CL-Fc, VL3-L5-VH3-L6-CH1-L7-CL-L8-Fc, VH3 and a second polypeptide having a structure represented by VH3-L5-VL3-L6-CH1-CL-Fc; VH3-L5-VL3-L6-CH1-L7-CL-Fc; or VH3-L5-VL3-L6-CH1-L7-CL-L8-Fc; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL3 is VH1 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1;CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, and L8 are amino acid linkers.

[0137] In some embodiments, the invention provides VL1-VL2-VH2-VH1-CH1-Fc, VH1-VH2-VL2-VL1-CH1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-CH1-Fc, VH1-L1-VH2-L2-VL2-L3-VH1-CH1 -Fc, VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc, VH1-L1-VH2-L2-VL2-L3- VH1-L4-CH1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc, VH1-L1-VH 2-L2-VL2-L3-VH1-L4-CH1-L5-Fc, VL1-VL2-VH2-VH1-CL-Fc, VH1-VH2-V L2-VL1-CL-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-CL-Fc, VH1-L1-VH2-L2-VL2 -L3-VH1-CL-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc, VH1-L1-VH2-L2-VL2-L3-VH1-L4-CL-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc, or a first polypeptide having a structure represented by VH1-L1-VH2-L2-VL2-L3-VH1-L4-CL-L5-Fc; and VL3-VH3-CL-Fc, VL3-L6-VH3-L7-CL-Fc, VL3-L6-VH3-L7-CL-L8-Fc, VH3-VL3-CL-Fc, VH3-L6-VL3-L7-CL-Fc, VH3-L6-VL3-L7-CL-L8-Fc, VL3-VH3-CH1-Fc, VL3-L6-VH3-L7-CH1-Fc, VL3-L6-VH3-L7-CH1-Fc, VL3-L6-VH3-L7-CH1-L8-Fc, VH3-VL3 and a second polypeptide having a structure represented by VH3-L6-VL3-L7-CH1-Fc, VH3-L6-VL3-L7-CH1-L8-Fc, wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein;VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region that includes immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, and L8 are amino acid linkers;

[0138] In some embodiments, the invention provides VL1-VL2-VH2-VH1-CL-CH1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-CL-CH1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-CH1-Fc, VL1-L1- VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc, VH1-VH2-VL2-VL1-CL-CH1-Fc, VH1-L1-VH2-L2-VL2 -L3-VL1-CL-CH1-Fc, VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-CH1-Fc, VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-Fc, VH1-L1-VH2-L2-VL2-L3-VL1 -L4-CL-L5-CH1-L6-Fc, VL1-VL2-VH2-VH1-CH1-CL-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-CH1-CL-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-CL-Fc, VL1 -L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc, VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc, VH1-VH2-VL2-VL1-CH1-CL-Fc, VH1-L1-VH2-L2 -VL2-L3-VL1-CH1-CL-Fc, VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-CL-Fc, VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc, or VH1-L1-VH2-L2-VL2 - The present invention is directed to an antigen-binding polypeptide complex (e.g., an antibody or antigen-binding fragment thereof) comprising a first polypeptide having a structure represented by VL3-VL1-L4-CH1-L5-CL-L6-Fc, and a second polypeptide having a structure represented by VL3-VH3-Fc, VL3-L7-VH3-Fc, VL3-L7-VH3-L8-Fc, VH3-VL3-Fc, VH3-L7-VL3-Fc, or VH4-L7-VL3-L8-Fc; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein;VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region that includes immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, and L8 are amino acid linkers.

[0139] In other aspects, the invention is directed to antigen-binding polypeptides and antigen-binding polypeptide complexes comprising a polypeptide having a structure represented by VL1-VL2-VL3-VH3-VH2-VH1; VH1-VH2-VH3-VL3-VL2-VL1; VL1-VH2-VL3-VH3-VL2-VH1; VH1-VL2-VH3-VL3-VH2-VL1; VL1-VL2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VH2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VH2-VH3-VL3-VL2-VH1; or VH1-VL2-VL3-VH3-VH2-VL1. In some aspects, the antigen-binding polypeptide or antigen-binding polypeptide complex contains an amino acid linker between any two regions depicted in the structures described herein. In some embodiments, the antigen-binding polypeptide or antigen-binding polypeptide complex can contain an Fc region, a CH1 region, or a CL region, or any combination thereof. In some embodiments, the antigen-binding polypeptide complex is an antibody, or an antigen-binding fragment thereof.

[0140] In some embodiments, the antigen-binding polypeptide of the antigen-binding polypeptide complex of the invention is selected from the group consisting of VL1-VL2-VL3-VH3-VH2-VH1; VH1-VH2-VH3-VL3-VL2-VL1; VL1-VH2-VL3-VH3-VL2-VH1; VH1-VL2-VH3-VL3-VH2-VL1; VL1-VL2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VL2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VH2-VH3-VL3-VL2-VH1; VH1 -VL2-VL3-VH3-VH2-VL1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1;VL1-L1- VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5- VH1; VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1; VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1; or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein. VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, L3, L4, and L5 are amino acid linkers.

[0141] In some embodiments, the antigen-binding polypeptide complex comprises a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VL3-VH3-VH2-VH1; VH1-VH2-VH3-VL3-VL2-VL1; VL1-VH2-VL3-VH3-VL2-VH1; VH1-VL2-VH3-VL3-VH2-VL1; VL1-VL2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VL2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VH2-VH3-VL3-VL2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VH2-VH3-VL3-VL2-VH1; VH1-VL2-VL3-VH3- VH2-VL1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1;VH1-L1-VH2-L2 -VH3-L3-VL3-L4-VL2-L5-VL1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5- VH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1;VL1-L1-VL2-L2-VH3 -L3-VL3-L4-VH2-L5-VH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1; VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1; or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1; the second polypeptide has a structure represented by VL4-VH4; VH4-VL4; VL4-L6-VH4; VH4-L6-VL4; VL4-L6-VH4-L7; VH4-L6-VL4-L7; VL4-VL5-VH5-VH4; VH4-VH5-VL5-VL4; VL4-L6-VL5-L7-VH5-L8-VH4; VH4-L6-VH5-L7-VH5-L8-VH4; L5-L8-VL4;VL4-VL5-VL6-VH6-VH5-VH4;VH4-VH5-VH6-VL6-VL5-VL4;VL 4-VH5-VL6-VH6-VL5-VH4;VH4-VL5-VH6-VL6-VH5-VL4;VL4-VL5-VH6-VL6 -VH5-VH4;VH4-VH5-VL6-VH6-VL5-VL4;VL4-VH5-VH6-VL6-VL5-VH4;VH4 -VL5-VL6-VH6-VH5-VL4;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4;VH4-L6-VL5-L7-VH6-L8-VL6 -L9-VH5-L10-VL4;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4;VL4-L6-V H5-L7-VH6-L8-VL6-L9-VL5-L10-VH4; or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein. VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL5 is a fifth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL6 is a sixth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH5 is a fifth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH6 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, L3, L4, L5, L6, L7, L8, L9, and L10 are amino acid linkers.

[0142] In some embodiments, antigen binding polypeptide or antigen binding polypeptide complex is VL1-VL2-VL3-VH3-VH2-VH1-Fc;VH1-VH2-VH3-VL3-VL2-VL1-Fc;VL1-VH2-VL3-VH3-VL2-VH1-Fc;VH1 -VL2-VH3-VL3-VH2-VL1-Fc;VL1-VL2-VH3-VL3-VH2-VH1-Fc;VH1-VH2-VL3-VH3-VL2-VL1-Fc;VL1-VH2-VH3-VL3-VL2-VH1-Fc;VH1-VL2-VL3-VH3-V H2-VL1-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc;VH1-L1-VH2-L2-VH3-L3-VL3- L4-VL2-L5-VL1-Fc;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-Fc;VL1-L1-VH2-L2-VL3- L3-VH3-L4-VL2-L5-VH1-L6-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc;VL1-L1-V L2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-Fc;V H1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-V H1-L6-Fc; VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc; or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc contains a polypeptide having the structure represented by;VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region that includes immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, and L6 are amino acid linkers;

[0143] In some embodiments, the antigen-binding polypeptide or antigen-binding polypeptide complex is VL1-VL2-VL3-VH3-VH2-VH1-Fc-Fc; VH1-VH2-VH3-VL3-VL2-VL1-Fc-Fc; VL1-VH2-VL3-VH3-VL2-VH1-Fc-Fc; VH1-VL2-VH3-VL3-VH2-VL1-Fc-Fc; VL1-VL2-VH3-VL3-VH2-VH1-Fc-Fc; VH1-VH2-VL3-VH3-VL2-VL1-Fc-Fc; VL1-VH2-VH3-VL3-VL2-VH1-Fc-Fc; VH1-VL2-VL3-VH3-VH2-VL1-Fc-Fc; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-Fc-Fc; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc-Fc; VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc-L7-Fc; VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc-Fc; VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-Fc-Fc; VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-Fc-L7-Fc; VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-Fc-Fc; VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc-Fc; VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc-L7-Fc; VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc-Fc; VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc-Fc; VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc-L7-Fc; VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc-Fc; VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc-Fc; VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc-L7-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-Fc-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc-Fc;VH1-L1-V H2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc-L7-Fc;L1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc-Fc;VL1-L1-VH2-L2- VH3-L3-VL3-L4-VL2-L5-VH1-L6-Fc-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-Fc-L7-Fc;VH1-L1-VL2-L2-VL 3-L3-VH3-L4-VH2-L5-VL1-Fc-Fc;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc-Fc; The polypeptide comprises a polypeptide having a structure represented by VH3-L4-VH2-L5-VL1-L6-Fc-L7-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising an immunoglobulin heavy chain constant region 2 (CH2), an immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers.

[0144] In some embodiments, the antigen-binding polypeptide complex includes polypeptide 1 and polypeptide 2; polypeptide 1 is VL1-VL2-VL3-VH3-VH2-VH1-Fc; -VH3-VL2-VH1-Fc;VH1-VL2-VH3-VL3-VH2-VL1-Fc;VL1-VL2-VH3-VL3-VH2-VH1-Fc;VH1-VH2-VL3-VH3-VL2-VL1-Fc;VL1-VH2-VH3-VL3-VL2-VH1-Fc ;VH1-VL2-VL3-VH3-VH2-VL1-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc;VH1-L1-V H2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-Fc;VL1 -L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1- L6-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL 2-L5-VL1-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-Fc;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc;or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc;The second polypeptide is VL4-VH4-Fc; VH4-VL4-Fc; VL4-L7-VH4-Fc; VH4-L7-VL4-Fc; VL4-L7-VH4-L8-Fc; VH4-L7-VL4-L8-Fc; VL4-CL-VH4-CH1-Fc; VH4-CL-VL4-CH1-Fc; VL4-CH1-VH4-CL-Fc; VH4-CH1-VL4-CL-Fc; VL4-L7-CL-L8-VH4-L9-CH1-Fc; VL4-L7-CL-L8-VH4-L9-CH1-L10-Fc; VH4-L7-CL-L8-VL4-L9-CH1-Fc; VH4-L7-CL-L8-VL4-L9-CH1-L10-Fc; VL4-L7-CH1-L8-VH4-L9-CL-Fc; VL4-L7-CH1-L8-VH4-L9-CL-L10-Fc; VH4-L7-CH1-L8-VL4-L9-CL-Fc; VH4-L7-CH1-L8-VL4-L9-CL-L10-Fc; VL4-VL5-VH5-VH4-Fc; VH4-VH5-VL5-VL4-Fc; VL4-L7-VL5-L8-VH5-L9-VH4-Fc; VH4-L7-VH5-L8-VL5-L9-VL4-Fc; VL4-L7-VL5-L8-VH5-L9-VH4-L10-Fc; VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc; VL4-VL5-VL6-VH6-VH5-VH4-Fc; VH4-VH5-VH6-VL6-VL5-VL4-Fc; VL4-VH5-VL6-VH6-VL5-VH4-Fc; VH4-VL5-VH6-VL6-VH5-VL4-Fc; VL4-VL5-VH6-VL6-VH5-VH4-Fc; VH4-VH5-VL6-VH6-VL5-VL4-Fc; VL4-VH5-VH6-VL6-VL5-VH4-Fc; VH4-VL5-VL6-VH6-VH5-VL4-Fc; VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc; VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc; VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc; VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc; VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc;VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc;VL4-L7-VH5-L8-VH6 -L9-VL6-L10-VL5-L11-VH4-Fc;VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L 11-VL4-Fc;VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc;VH4 -L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc;VL4-L7-VH5-L8-VL6 -L9-VH6-L10-VL5-L11-VH4-L12-Fc;VH4-L7-VL5-L8-VH6-L9-VL6-L10-V H5-L11-VL4-L12-Fc;VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12 -Fc;VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc;VL4-L7-VH 5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc; or VH4-L7-VL5-L8-VL6-L9 -having a structure represented by VH6-L10-VH5-L11-VL4-L12-Fc; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL5 is a fifth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL6 is a sixth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and VH5 is a fifth immunoglobulin heavy chain variable region that specifically binds to an HIV protein;VH6 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region that includes immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, and L12 are amino acid linkers;

[0145] <h2 style=";text-align:left;direction:ltr">VL1-VL2-VL3-VH3-VH2-VH1-CH1-CL;VL1-VL 2-VL3-VH3-VH2-VH1-CL-CH1;VH1-VH2-VH3-VL3-VL2-VL1-CH1-CL;VH1- VH2-VH3-VL3-VL2-VL1-CL-CH1;VL1-VH2-VL3-VH3-VL2-VH1-CH1-CL;VL1-VH2-VL3-VH3-VL2-VH1-CL-CH1;VH1-VL2-VH3-VL3-VH2-VL1-CH1-CL VH1-VL2-VH3-VL3-VH2-VL1-CL-CH1;VL1-VL2-VH3-VL3-VH2-VH1-CH1-CL;VL1-VL2-VH3-VL3-VH2-VH1-CL-CH1 H1-CL;VH1-VH2-VL3-VH3-VL2-VL1-CL-CH1;VL1-VH2-VH3-VL3-VL2-VH1-CH1-CL;VL1-VH2-VH3-VL3-VL2-VH1-CL-CH1;VH1-VL2-VL3-VH3-VH2- VL1-CH1-CL;VH1-VL2-VL3-VH3-VH2-VL1-CL-CH1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1-CL;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1-CL;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL-CH1;VL1-L1 -VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-L7-CH1;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1-CL;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1-CL;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1-L7-CL;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL-CH1;<h2 style=";text-align:left;direction:ltr">VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL-CH1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1-L7-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-CH1;V L1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL-CH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH1-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH1-L7-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-CH1;VH1 -L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-CH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-L7-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-CL L;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-L7-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-L7-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CL-CH1;VH1-L1-VH2-L2-VL3-L3-V H3-L4-VL2-L5-VL1-L6-CL-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL-L7-CH1;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1 -CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-L7-CL;VL1-L1-VH2-L2-VH 3-L3-VL3-L4-VL2-L5-VH1-CL-CH1;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL 2-L5-VH1-L6-CL-CH1;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6- CL-L7-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-CL;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1-CL;VH1-L1-VL2-L2-VL 3-L3-VH3-L4-VH2-L5-VL1-L6-CH1-L7-CL;VH1-L1-VL2-L2-VL3-L3-VH3 -L4-VH2-L5-VL1-CL-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1- or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CL-L7-CH1; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; and VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein;VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is heavy chain constant region 1; CL is a light chain constant region; and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers.

[0146] In some embodiments, the antigen-binding polypeptide complex includes polypeptide 1 and polypeptide 2; -VH3-VH2-VH1-CH1-CL;VL1-VL2-VL3-VH3-VH2-VH1-CL-CH1;VH1-VH2-VH3-VL3-VL2-VL1-CH1;VH1-VH2-VH3-VL3-VL2-VL1-CL;VH1-VH2-VH3-VL3-VL 2-VL1-CH1-CL;VH1-VH2-VH3-VL3-VL2-VL1-CL-CH1;VL1-VH2-VL3-VH3-VL2-VH1-CH1;VL1-VH2-VL3-VH3-VL2-VH1-CL;VL1-VH2-VL3-VH3-VL2-VH1-C H1-CL;VL1-VH2-VL3-VH3-VL2-VH1-CL-CH1;VH1-VL2-VH3-VL3-VH2-VL1-CH1;VH1-VL2-VH3-VL3-VH2-VL1-CL;VH1-VL2-VH3-VL3-VH2-VL1-CH1-CL;VH 1-VL2-VH3-VL3-VH2-VL1-CL-CH1;VL1-VL2-VH3-VL3-VH2-VH1-CH1;VL1-VL2-VH3-VL3-VH2-VH1-CL;VL1-VL2-VH3-VL3-VH2-VH1-CH1-CL;VL1-VL2-V H3-VL3-VH2-VH1-CL-CH1;VH1-VH2-VL3-VH3-VL2-VL1-CH1;VH1-VH2-VL3-VH3-VL2-VL1-CL;VH1-VH2-VL3-VH3-VL2-VL1-CH1-CL;VH1-VH2-VL3-VH3- VL2-VL1-CL-CH1;VL1-VH2-VH3-VL3-VL2-VH1-CH1;VL1-VH2-VH3-VL3-VL2-VH1-CL;VL1-VH2-VH3-VL3-VL2-VH1-CH1-CL;VL1-VH2-VH3-VL3-VL2-VH1 -CL-CH1;VH1-VL2-VL3-VH3-VH2-VL1-CH1;VH1-VL2-VL3-VH3-VH2-VL1-CL;VH1-VL2-VL3-VH3-VH2-VL1-CH1-CL;VH1-VL2-VL3-VH3-VH2-VL1-CL-CH1;<h2 style=";text-align:left;direction:ltr">VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1-CL;VL1-L1-VL2-L2-VL3-L3-VH 3-L4-VH2-L5-VH1-L6-CH1-CL;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1-L7-CL;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL-CH1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-CH1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-L7-CH1;VH1-L1-VH2-L2-VH3-L3- VL3-L4-VL2-L5-VL1-CH1;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1 -CL;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1-L7-CL;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL-CH1;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL-CH1;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL-L7-CH1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1;<h2 style=";text-align:left;direction:ltr">VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1-CL;VL1-L1-VH2-L2-VL3- L3-VH3-L4-VL2-L5-VH1-L6-CH1-L7-CL;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-CH1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL-CH1;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL-L7-CH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1;VH1-L1-VL2-L2-VH3-L3-VL 3-L4-VH2-L5-VL1-L6-CH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH1-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6 -CH1-L7-CL;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-CH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-CH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-L7-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1;<h2 style=";text-align:left;direction:ltr">VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-CL;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-L7-CL;VL1-L1-VL2- L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-CH1;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-L7-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1;VH1-L1-VH2-L2-VL3-L3- VH3-L4-VL2-L5-VL1-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-L7-CL;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2- L5-VL1-CL-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL-CH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL-L7-CH1;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL;<h2 style=";text-align:left;direction:ltr">VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-L7-CL;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL-CH1;VL1-L1-VH 2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL-CH1;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL-L7-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL;VH1-L1-VL2-L2-VL3-L3-VH3 -L4-VH2-L5-VL1-L6-CL;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-CL;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1-CL;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1-L7-CL;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L 5-VL1-L6-CL-CH1;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6- VL4-VH4-CL;VL4-VH 4-CH1-CL;VL4-VH4-CL-CH1;VH4-VL4-CH1;VH4-VL4-CL;VH4-VL4-CH1-CL;VH4-VL4-CL-CH1;VL4-L8-VH4-CH1;VL4-L8-VH4-CL;VL4-L8-VH4-CH1-CL;VL4-L8-VH4-CL-CH1;VH4-L8-VL4-CH1;VH4-L8-VL4-CL;VH4-L8-VH4-CH1-CL;VH4-L8-VH4-CL-CH1;VL4-VL5-VH5-VH4-CH1;VL4-VL5-VH5-VH4-CL;VL4-VL5-VH5-VH4-CH1-CL;VL4-VL5-VH5-VH4-CL-CH1;VH4-VH5-VL5-VL4-CH; 1;VH4-VH5-VL5-VL4-CL;VH4-VH5-VL5-VL4-CH1-CL;VH4-VH5-VL5-VL4-CL-CH1;VL4-L8-VL5-L9-VH5-L10-VH4-CH1;VL4-L8-VL5-L9-VH5-L10-VH4-CL;VL4-L8-VL5-L9-VH5-L10-VH4-CH1-CL;VL4-L8-VL5-L9-VH5-L10-VH4-CL-CH1;VH4-L8-VH5-L9-VL5-L10-VL4-CH1;VH4-L8-VH5-L9-VL5-L10-VL4-CL;VH4-L8-VH5-L9-VL5-L10-VL4-CH1-CL;VH4-L8-VH5-L9-VL5-L10-VL4-CL-CH1;VL4-VL5-VL6-VH6-VH5-VH4-CH1;VL4-VL5-VL6-VH6-VH5-VH4-CL;VL4-VL5-VL6-VH6-VH5-VH4-CH1-CL;VL4-VL5-VL6-VH6-VH5-VH4-CL-CH1;VH4-VH5-VH6-VL6-VL5-VL4-CH1;VH4-VH5-VH6-VL6-VL5-VL4-CL;VH4-VH5-VH6-VL6-VL5-VL4-CH1-CL;VH4-VH5-VH6-VL6-VL5-VL4-CL-CH1;VL4-VH5-VL6-VH6-VL5-VH4-CH1;VL4-VH5-VL6-VH6-VL5-VH4-CL;VL4-VH5-VL6-VH6-VL5-VH4-CH1-CL;VL4-VH5-VL6-VH6-VL5-VH4-CL-CH1;VH4-VL5-VH6-VL6-VH5-VL4-CH1;VH4-VL5-VH6-VL6-VH5-VL4-CL;VH4-VL5-VH6-VL6-VH5-VL4-CH1-CL;VH4-VL5-VH6-VL6-VH5-VL4-CL-CH1;VL4-VL5-VH6-VL6-VH5-VH4-CH1;VL4-VL5-VH6-VL6-VH5-VH4-CL;VL4-VL5-VH6-VL6-VH5-VH4-CH1-CL;VL4-VL5-VH6-VL6-VH5-VH4-CL-CH1;VH4-VH5-VL6-VH6-VL5-VL4-CH1;VH4-VH5-VL6-VH6-VL5-VL4-CL;VH4-VH5-VL6-VH6-VL5-VL4-CH1-CL;VH4-VH5-VL6-VH6-VL5-VL4-CL-CH1;VL4-VH5-VH6-VL6-VL5-VH4-CH1;VL4-VH5-VH6-VL6-VL5-VH4-CL;VL4-VH5-VH6-VL6-VL5-VH4-CH1-CL;VL4-VH5-VH6-VL6-VL5-VH4-CL-CH1;VH4-VL5-VL6-VH6-VH5-VL4-CH1;VH4-VL5-VL6-VH6-VH5-VL4-CL;VH4-VL5-VL6-VH6-VH5-VL4-CH1-CL;VH4-VL5-VL6-VH6-VH5-VL4-CL-CH1;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CH1;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CL;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CH1-CL;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CL-CH1;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CH1;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CL;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CH1-CL;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CL-CH1;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CH1;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CL;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CH1-CL;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CL-CH1;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CH1;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L11-VL4-CL;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CH1-CL;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CL-CH1;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CH1;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CL;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CH1-CL;VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CL-CH1;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CH1;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CL;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CH1-CL;VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CL-CH1;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CH1;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CL;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CH1-CL;VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CL-CH1;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CH1;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CL;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CH1-CL;VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CL-CH1;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CH1;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CL;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CH1-CL;VL4-L8-VL5-L9 -VH6-L10-VL6-L11-VH5-L12-VH4-CL-CH1;VH4-L8-VH5-L9-VL6-L10-VH6-L 11-VL5-L12-VL4-CH1;VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-C L;VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-CH1-CL;VH4-L8-VH5-L 9-VL6-L10-VH6-L11-VL5-L12-VL4-CL-CH1;VL4-L8-VL5-L9-VH6-L10-VL6 -L11-VH5-L12-VH4-L13-CH1;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12- VH4-L13-CL;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-L13-CH1-C L;VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-L13-CL-CH1;VH4-L8-V H5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CH1; VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CL; VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CH1-CL; or VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CL-CH1; VL1 being a first immunoglobulin light chain variable region that specifically binds to an HIV protein. VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL5 is a fifth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL6 is a sixth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein;VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH5 is a fifth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH6 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is heavy chain constant region 1; CL is the light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, and L13 are amino acid linkers;

[0147] In some embodiments, the antigen-binding polypeptide complex includes polypeptide 1 and polypeptide 2; polypeptide 1 is VL1-VL2-VL3-VH3-VH2-VH1-CH1-Fc; -VH2-VL3-VH3-VL2-VH1-CH1-Fc;VH1-VL2-VH3-VL3-VH2-VL1-CH1-Fc;VL1-VL2-VH3-VL3-VH2-VH1-CH1-Fc;VH1-VH2-VL3-VH3-VL2-VL1-CH1-Fc;VL1 -VH2-VH3-VL3-VL2-VH1-CH1-Fc;VH1-VL2-VL3-VH3-VH2-VL1-CH1-Fc;VL1-VL2-VL3-VH3-VH2-VH1-CL-Fc;VH1-VH2-VH3-VL3-VL2-VL1-CL-Fc;VL1- VH2-VL3-VH3-VL2-VH1-CL-Fc;VH1-VL2-VH3-VL3-VH2-VL1-CL-Fc;VL1-VL2-VH3-VL3-VH2-VH1-CL-Fc;VH1-VH2-VL3-VH3-VL2-VL1-CL-Fc;VL1-VH2- VH3-VL3-VL2-VH1-CL-Fc;VH1-VL2-VL3-VH3-VH2-VL1-CL-Fc;VL1-VL2-VL3-VH3-VH2-VH1-CH1-CL-Fc;VH1-VH2-VH3-VL3-VL2-VL1-CH1-CL-Fc;VL1 -VH2-VL3-VH3-VL2-VH1-CH1-CL-Fc;VH1-VL2-VH3-VL3-VH2-VL1-CH1-CL-Fc;VL1-VL2-VH3-VL3-VH2-VH1-CH1-CL-Fc;VH1-VH2-VL3-VH3-VL2-VL1-C H1-CL-Fc;VL1-VH2-VH3-VL3-VL2-VH1-CH1-CL-Fc;VH1-VL2-VL3-VH3-VH2-VL1-CH1-CL-Fc;VL1-VL2-VL3-VH3-VH2-VH1-CL-CH1-Fc;VH1-VH2-VH3- VL3-VL2-VL1-CL-CH1-Fc;VL1-VH2-VL3-VH3-VL2-VH1-CL-CH1-Fc;VH1-VL2-VH3-VL3-VH2-VL1-CL-CH1-Fc;VL1-VL2-VH3-VL3-VH2-VH1-CL-CH1-Fc;<h2 style=";text-align:left;direction:ltr">VH1-VH2-VL3-VH3-VL2-VL1-CL-CH1-Fc;VL1-VH2-VH3-VL3-VL2-VH1-CL-CH1-Fc;VH1-VL2-VL3-VH3-VH2-VL1-CL-CH1-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1-Fc;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1-Fc;VL1-L1-VH2-L2-VL3-L3-VL3-L4-VL2-L5-VH1-CH1-Fc;VH1- L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-Fc;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-Fc;VL1-L1-VL2-L2-VL3- L3-VH3-L4-VH2-L5-VH1-CL-Fc;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL 1-CL-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL-Fc;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1-CL-Fc;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1-CL-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-CL-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-CL-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1-CL-Fc;VH1-L1-VH2-L2-VL3-L3-VH3- L4-VL2-L5-VL1-CH1-CL-Fc;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-CL-Fc;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-CL-Fc;V L1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL-CH1-Fc;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL-CH1-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L 4-VL2-L5-VH1-CL-CH1-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-CH1-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-CH1-Fc;VH1 -L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CL-CH1-Fc; VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL-CH1-Fc; orVH1-L1-VL2-L2-VL3-L3-VH3- L4-VH2-L5-VL1-CL-CH1-Fc has the structure shown by; CH1-Fc;VH4-VL4-CL-Fc;VH4-VL4-CH1-CL-Fc;VH4-VL4-CL-CH1-Fc;VL4-L6-VH4-CH1-Fc;VL4-L6-VH4-CL-Fc;VL4-L6-VH4-CH1-CL-Fc;VL4-L6-VH4 -CL-CH1-Fc;VH4-L6-VL4-CH1-Fc;VH4-L6-VL4-CL-Fc;VH4-L6-VL4-CH1-CL-Fc;VH4-L6-VL4-CL-CH1-Fc;VL4-CL-VH4-CH1-Fc;VH4-CL-VL4-CH1-Fc;<h2 style=";text-align:left;direction:ltr">VL4-CH1-VH4-CL-Fc;VH4-CH1-VL4-CL-Fc;VL4-L6-CL-L7-VH4-L8-CH1-Fc;VL4-L6-CL-L7-VH4-L8-CH1-L9-Fc;VH4-L6-CL-L7-VL4-L8-CH1-Fc;VH4-L6-CL-L7-VL4-L8-CH1-L9-Fc;VL4-L6-CH1-L7-VH4-L8-CL-Fc;VL4-L6-CH1-L7-VH4-L8-CL-Fc;VL4-L6-CH1-L7-VH4-L8-CL-L9-Fc;VH4-L6-CH1-L7-VL4-L8-CL-Fc;VH4-L6-CH1-L7 L7-VL4-L8-CL-L9-Fc;VL4-VL5-VH5-VH4-CH1-Fc;VL4-VL5-VH5-VH4-CL-Fc;VL4-VL5-VH5-VH4-CH1-CL-Fc;VL4-VL5-VH5-VH4-CL-CH1-Fc;VH4-VH5 VL5-VL4-CH1-Fc;VH4-VH5-VL5-VL4-CL-Fc;VH4-VH5-VL5-VL4-CH1-CL-Fc; L4-L6-VL5-L7-VH5-L8-VH4-CL-Fc;VL4-L6-VL5-L7-VH5-L8-VH4-CH1-CL-Fc;VL4-L6-VL5-L7-VH5-L8-VH4-CL-CH1-Fc;VH4-L6-VH5-L7-VL5-L8-VL4-CH1-Fc;VH4-L6-VH5-L7-VL5-L8-VL4-CH1-Fc;VH4-L6-VH5-L7-VL5-L8-VL4-CL-Fc;VH4-L6-VH5-L7-VL5-L8-VL4-CH1-CL-Fc;VH4-L6-VH5-L7-VL5-L8-VL4-CH1-CL-Fc;VH4-L6-VH5-L7-VL5-L8-VL4-CL-CH1-Fc;VL4-VL5-VL6- VH6-VH5-VH4-CH1-Fc;VL4-VL5-VL6-VH6-VH5-VH4-CL-Fc;VL4-VL5-VL6- VH6-VH5-VH4-CH1-CL-Fc;VL4-VL5-VL6-VH6-VH5-VH4-CL-CH1-Fc;VH4-VH 5-VH6-VL6-VL5-VL4-CH1-Fc;VH4-VH5-VH6-VL6-VL5-VL4-CL-Fc;VH4-VH 5-VH6-VL6-VL5-VL4-CH1-CL-Fc;VH4-VH5-VH6-VL6-VL5-VL4-CL-CH1-Fc;VL4-VH5-VL6-VH6-VL5-VH4-CH1-Fc;VL4-VH5-VL6-VH6-VL5-VH4-CL-Fc;VL4-VH5-VL6-VH6-VL5-VH4-CH1-CL-Fc;VL4-VH5-VL6-VH6-VL5-VH4-CL-CH1-Fc;VH4-VL5-VH6-VL6-VH5-VL4-CH1-Fc;VH4-VL5-VH6-VL6-VH5-VL4-CL-Fc;VH4-VL5-VH6-VL6-VH5-VL4-CH1-CL-Fc;VH4-VL5-VH6-VL6-VH5-VL4-CL-CH1-Fc;VL4-VL5-VH6-VL6-VH5-VH4-CH1-Fc;VL4-VL5-VH6-VL6-VH5-VH4-CL-Fc;VL4-VL5-VH6-VL6-VH5-VH4-CH1-CL-Fc;VL4-VL5-VH6-VL6-VH5-VH4-CL-CH1-Fc;VH4-VH5-VL6-VH6-VL5-VL4-CH1-Fc;VH4-VH5-VL6-VH6-VL5-VL4-CL-Fc;VH4-VH5-VL6-VH6-VL5-VL4-CH1-CL-Fc;VH4-VH5-VL6-VH6-VL5-VL4-CL-CH1-Fc;VL4-VH5-VH6-VL6-VL5-VH4-CH1-Fc;VL4-VH5-VH6-VL6-VL5-VH4-CL-Fc;VL4-VH5-VH6-VL6-VL5-VH4-CH1-CL-Fc;VL4-VH5-VH6-VL6-VL5-VH4-CL-CH1-Fc;VH4-VL5-VL6-VH6-VH5-VL4-CH1-Fc;VH4-VL5-VL6-VH6-VH5-VL4-CL-Fc;VH4-VL5-VL6-VH6-VH5-VL4-CH1-CL-Fc;VH4-VL5-VL6-VH6-VH5-VL4-CL-CH1-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CH1-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CL-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CH1-CL-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CL-CH1-Fc;<h2 style=";text-align:left;direction:ltr">VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CH1-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CL-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CH1-CL-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CL-CH1-Fc;VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CL-CH1-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L;<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> 9-VL5-L10-VH4-CH1-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-CL-Fc;VL4-L6-VH5-L7<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr">-VL6-L8-VH6-L9-VL5-L10-VH4-CH1-CL-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-CL-CH1-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CH1-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CL-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CL-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CH1 ...6-V L5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CL-CH1-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CH1-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CL-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CL-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CH1-CL-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CL-CH1-Fc;VH4 -L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CH1-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CL-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CH1-CL-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CL-CH1-Fc;V L4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CL-Fc;VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CH1-CL-Fc;VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CL-CH1-Fc;VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CH1-Fc;VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CL-Fc;<h2 style=";text-align:left;direction:ltr">VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CH1-CL-Fc;VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CL-CH1-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CH1-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CL-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-C H1-CL-Fc;VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CL-CH1-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CH1-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CL-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CL-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CH1-CL-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CH1-CL-Fc;VH4-L6-VH5-L7-VH6-L8-VL6-L9-V L5-L10-VL4-L11-CL-CH1-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CH1-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CL-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CL-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CH1-CL-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CH1-CL-Fc;VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CL-CH1-Fc;VH4-L6-VL5-L7 -VH6-L8-VL6-L9-VH5-L10-VL4-L11-CH1-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-L11-CL-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-L11-CH1-CL-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-L11-CH1-CL-Fc;VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-L11-CL-CH1-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-L11-CH1-Fc;VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-L11-CL-Fc;VL4-L6-VL5 -L7-VH6-L8-VL6-L9-VH5-L10-VH4-L11-CH1-CL-Fc;VL4-L6-VL5-L7-VH 6-L8-VL6-L9-VH5-L10-VH4-L11-CL-CH1-Fc;VH4-L6-VH5-L7-VL6-L8-V H6-L9-VL5-L10-VL4-L11-CH1-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5- L10-VL4-L11-CL-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-L11-CH1-CL-Fc;VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-L11-CL-C H1-Fc;VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-L11-CH1-Fc;VL4 -L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-L11-CL-Fc;VL4-L6-VH5-L7- VH6-L8-VL6-L9-VL5-L10-VH4-L11-CH1-CL-Fc;VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-L11-CL-CH1-Fc;VH4-L6-VL5-L7-VL6-L8-VH6-L 9-VH5-L10-VL4-L11-CH1-Fc;VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10 -VL4-L11-CL-Fc;VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11-CH or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11-CL-CH1-Fc; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein;VL5 is a fifth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL6 is a sixth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein. VH5 is a fifth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH6 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region that includes immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is heavy chain constant region 1; CL is a light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, and L11 are amino acid linkers.

[0148] <h2 style=";text-align:left;direction:ltr">VL1-VL2-VL3-VH3-VH2-VH1-CH3-CH3;VH1-VH2-VH3-VL3 -VL2-VL1-CH3-CH3;VL1-VH2-VL3-VH3-VL2-VH1-CH3-CH3;VH1-VL2-VH3-V L3-VH2-VL1-CH3-CH3;VL1-VL2-VH3-VL3-VH2-VH1-CH3-CH3;VH1-VH2-VL3-VH3-VL2-VL1-CH3-CH3;VL1-VH2-VH3-VL3-VL2-VH1-CH3-CH3;VH1-VL2-VL 3-VH3-VH2-VL1-CH3-CH3;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH3-CH3;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH3-CH3;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH3-CH3;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH3-CH3;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1- CH3-CH3;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH3-CH3;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH3-CH3;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH3-CH3;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH3-CH3;VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH3-CH3; VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH3-CH3;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH3-CH3;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH3-CH3;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH3-CH3;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH3-CH3;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH3-CH3;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH3-L7-CH3;V H1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH3-L7-CH3;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH3-L7-CH3; VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH3-L7-CH3;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH3-L7-CH 3;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH3-L7-CH3;VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH3-L7-C or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH3-L7-CH3; where VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH3 is immunoglobulin heavy chain constant region 3; and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers.

[0149] In some embodiments, an antigen-binding polypeptide complex of the invention comprises a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide is VL1-VL2-VL3-VH3-VH2-VH1; VH1-VH2-VH3-VL3-VL2-VL1; VL1-VH2-VL3-VH3-VL2-VH1; VH1-VL2-VH3-VL3-VH2-VL1; VL1-VL2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VL2-VH3-VL3-VH2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VH2-VH3-VL3-VL2-VH1; VH1-VH2-VL3-VH3-VL2-VL1; VL1-VH2-VH3-VL3-VL2-VH1; 2-VL3-VH3-VH2-VL1;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1;VH1- L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1;VL1-L1-VH2-L2-VL3-L3-VH3-L4 -VL2-L5-VH1;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1;VL1-L1-VL2- L2-VH3-L3-VL3-L4-VH2-L5-VH1;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5 -VL1; VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1; or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1; the second polypeptide has a structure represented by VL4-VL5; VL4-L6-VL5; VL4-VL5-VL6; or VL4-L6-VL5-L7-VL6; the third polypeptide has a structure represented by VH4-VH5; VH4-L6-VH5; VH4-VH5-VH6; or VH4-L6-VH5-L7-VH6. VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL5 is a fifth immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL6 is a sixth immunoglobulin light chain variable region that specifically binds to an HIV protein;VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH5 is a fifth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH6 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers;

[0150] In some embodiments, an antigen-binding polypeptide complex of the invention comprises a first polypeptide, a second polypeptide, and a third polypeptide; the first polypeptide is VL1-VL2-VL3-VH3-VH2-VH1-Fc; VH1-VH2-VH3-VL3-VL2-VL1-Fc; VL1-VH2-VL3-VH3-VL2-VH1-Fc; VH1-VL2-VH3-VL3-VH2-VL1-Fc; VL1-VL2-VH3-VL3-VH2-VH1-Fc; VL1-VL2-VH3-VL3-VH2-VH1-Fc; VH1-VH2-VL3-VH3-VL2-VL1-Fc; VH1-VH2-VL3-VH3-VL2-VL1-Fc; VL1-VH2-VH3-VL3-VH2-VH1-Fc; VL2-VH1-Fc;VH1-VL2-VL3-VH3-VH2-VL1-Fc;VL1-L1-VL2-L2-VL3-L3-VH3 -L4-VH2-L5-VH1-Fc;VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc; VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc;VH1-L1-VH2-L2-VH3-L3 -VL3-L4-VL2-L5-VL1-L6-Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1 -Fc;VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc;VH1-L1-VL2-L2 -VH3-L3-VL3-L4-VH2-L5-VL1-Fc;VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5 -VL1-L6-Fc;VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc;VL1-L1-VL 2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4 -VL2-L5-VL1-Fc;VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc;VL 1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc;VL1-L1-VH2-L2-VH3-L3-VL 3-L4-VL2-L5-VH1-L6-Fc;VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-F c; or having a structure represented by VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc;The second polypeptide is VL4-VL5;VL4-L7-VL5;VL4-CL;VL4-L7-CL;VL4-CH1;VL4-L7-CH1;VH4-VH5;VH4-L7-VH5;VH4-CL;VH4-L7-CL;VH4-CH1;VH4-L7-CH1;VL4-VL5-VL6;VL4-L7-VL5-L8-VL6;VL4-VL5-VL6-CL;VL4-L7-VL5-L8-VL6-CL;VL4-L7-VL5-L8-VL6-CL;VL4-L7-VL5-L8-VL6-L9-CL;VL4-VL5-VL6-CH1;VL4-L7-VL5-L8-VL6-CH1;V and the third polypeptide has a structure represented by VH4-VH5-Fc; VH4-L10-VH5-Fc; VH4-L10-VH5-L11-Fc; VH 4-CH1-Fc;VH4-L10-CH1-Fc;VH4-L10-CH1-L11-Fc;VH4-CL-Fc;VH4-L10-C L-Fc;VH4-L10-CL-L11-Fc;VH4-VH5-Fc;VH4-L10-VH5-Fc;VH4-L10-VH5-L 11-Fc;VH4-VH5-VH6-Fc;VH4-L10-VH5-L11-VH6-Fc;VH4-L10-VH5-L11-VH 6-L12-Fc;VH4-VH5-VH6-CH1-Fc;VH4-L10-VH5-L11-VH6-CH1-Fc;VH4-L10- VH5-L11-VH6-L12-CH1-Fc;VH4-L10-VH5-L11-VH6-L12-CH1-L13-Fc;VH4- VH5-VH6-CL-Fc;VH4-L10-VH5-L11-VH6-CL-Fc;VH4-L10-VH5-L11-VH6-L12 -CL-Fc;VH4-L10-VH5-L11-VH6-L12-CL-L13-Fc;VL4-VL5-VL6-Fc;VL4-L1 0-VL5-L11-VL6-Fc;VL4-L10-VL5-L11-VL6-L12-Fc;VL4-VL5-VL6-CH1-Fc;VL4-L10-VL5-L11-VL6-CH1-FcVL4-L10-VL5-L11-VL6-L12-CH1-Fc; VL4-L10-VL5-L11-VL6-L12-CH1-L13-Fc; VL4-VL5-VL6-CL-Fc; VL4-L10-VL5-L11-VL6-CL-Fc; VL4-L10-VL5-L11-VL6-L12-CL-Fc; or VL4-L10-VL5-L11-VL6-L12-CL-L13-Fc VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL5 is a fifth immunoglobulin light chain variable region that specifically binds to an HIV protein; VL6 is a sixth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH5 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; is a fifth immunoglobulin heavy chain variable region; VH6 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is heavy chain constant region 1; CL is a light chain constant region; Fc is a region that includes immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, and L13 are amino acid linkers;

[0151] In some embodiments, one or more of VH1, VH2, VH3, VH4, VH5, and VH6 of an antigen-binding polypeptide or antigen-binding polypeptide complex described herein can specifically bind to the same antigen or different antigens. In some embodiments, one or more of VL1, VL2, VL3, VL4, VL5, and VL6 of an antigen-binding polypeptide or antigen-binding polypeptide complex described herein can specifically bind to the same antigen or different antigens.

[0152] In some embodiments, VH1, VL1, VH4, and VL4 of an antigen-binding polypeptide or antigen-binding polypeptide complex described herein specifically bind to the same antigen. In some embodiments, VH2, VL2, VH5, and VL5 of an antigen-binding polypeptide or antigen-binding polypeptide complex described herein specifically bind to the same antigen. In some embodiments, VH3, VL3, VH6, and VL6 of an antigen-binding polypeptide or antigen-binding polypeptide complex described herein specifically bind to the same antigen. In some embodiments, VH1, VL1, VH4, and VL4 of an antigen-binding polypeptide or antigen-binding polypeptide complex described herein specifically bind to the same antigen; VH2, VL2, VH5, and VL5 of an antigen-binding polypeptide or antigen-binding polypeptide complex described herein specifically bind to the same antigen; and VH3, VL3, VH6, and VL6 of an antigen-binding polypeptide or antigen-binding polypeptide complex described herein specifically bind to the same antigen.

[0153] In some embodiments of the antigen-binding polypeptides or antigen-binding polypeptide complexes of the invention, VH1, VH2, and VH3 each comprise a heavy chain variable region derived from the PGT121 antibody, VRC01 antibody, 10E8v4 antibody, or PG16 antibody, or a variant thereof; and / or VL1, VL2, and VL3 each comprise a light chain variable region derived from the PGT121 antibody, VRC01 antibody, 10E8v4 antibody, or PG16 antibody, or a variant thereof.

[0154] In some embodiments of the antigen-binding polypeptides or antigen-binding polypeptide complexes of the invention, VH1, VH2, VH3, and VH4 each comprise a heavy chain variable region derived from the PGT121 antibody, VRC01 antibody, 10E8v4 antibody, or PG16 antibody, or a variant thereof; and / or VL1, VL2, VL3, and VL4 each comprise a light chain variable region derived from the PGT121 antibody, VRC01 antibody, 10E8v4 antibody, or PG16 antibody, or a variant thereof.

[0155] In some embodiments of the antigen-binding polypeptides or antigen-binding polypeptide complexes of the invention, VH1, VH2, VH3, VH4, and VH5 each comprise a heavy chain variable region derived from the PGT121 antibody, VRC01 antibody, 10E8v4 antibody, or PG16 antibody, or a variant thereof; and / or VL1, VL2, VL3, VL4, and VL5 each comprise a light chain variable region derived from the PGT121 antibody, VRC01 antibody, 10E8v4 antibody, or PG16 antibody, or a variant thereof.

[0156] In some embodiments of the antigen-binding polypeptides or antigen-binding polypeptide complexes of the invention, VH1, VH2, VH3, VH4, VH5, and VH6 each comprise a heavy chain variable region derived from the PGT121 antibody, VRC01 antibody, 10E8v4 antibody, or PG16 antibody, or a variant thereof; and / or VL1, VL2, VL3, VL4, VL5, and VL6 each comprise a light chain variable region derived from the PGT121 antibody, VRC01 antibody, 10E8v4 antibody, or PG16 antibody, or a variant thereof.

[0157] In some embodiments, VH1, VH2, and VH3 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 20-23; and / or VL1, VL2, and VL3 each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 24-27.

[0158] In some embodiments, VH1, VH2, VH3, and VH4 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 20-23; and / or VL1, VL2, VL3, and VL4 each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 24-27.

[0159] In some embodiments, VH1, VH2, VH3, VH4, and VH5 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 20-24; and / or VL1, VL2, VL3, VL4, and VL5 each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 24-27.

[0160] In some embodiments, VH1, VH2, VH3, VH4, VH5, and VH6 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 20-23; and / or VL1, VL2, VL3, VL4, VL5, and VL6 each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 24-27.

[0161] In some embodiments, the VH1, VH2, and VH3 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention each have a CDR1 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 60, 63, 66, and 69; a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 61, 64, 67, and 70; and a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 62, 65, 68, and 71. and VL1, VL2, and VL3 each comprise a CDR1 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 72, 75, 78, and 81; a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 73, 76, 79, and 82; and a CDR3 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 74, 77, 80, and 83.

[0162] In some embodiments, VH1, VH2, VH3, and VH4 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention each have a CDR1 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 60, 63, 66, and 69; a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 61, 64, 67, and 70; and a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 62, 65, 68, and 71. and VL1, VL2, VL3, and VL4 each comprise a CDR1 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 72, 75, 78, and 81; a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 73, 76, 79, and 82; and a CDR3 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 74, 77, 80, and 83.

[0163] In some embodiments, VH1, VH2, VH3, VH4, and VH5 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention each have a CDR1 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 60, 63, 66, and 69; a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 61, 64, 67, and 70; and a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 62, 65, 68, and 71. and VL1, VL2, VL3, VL4, and VL5 each comprise a CDR1 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 72, 75, 78, and 81; a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 73, 76, 79, and 82; and a CDR3 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 74, 77, 80, and 83.

[0164] In some embodiments, VH1, VH2, VH3, VH4, VH5, and VH6 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention each have a CDR1 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 60, 63, 66, and 69; a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 61, 64, 67, and 70; and a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 62, 65, 68, and 71. and VL1, VL2, VL3, VL4, VL5, and VL6 each comprise a CDR1 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 72, 75, 78, and 81; a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 73, 76, 79, and 82; and a CDR3 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 74, 77, 80, and 83.

[0165] Tetraspecific construct In yet another aspect, the present invention is directed to an antigen-binding polypeptide complex having a first polypeptide and a second polypeptide, the first polypeptide having a structure represented by VL1-VL2-VH2-VH1 or VH1-VH2-VL2-VL1, and the second polypeptide having a structure represented by VL3-VL4-VH4-VH3 or VH3-VH4-VL4-VL3. In some embodiments, the antigen-binding polypeptide complex contains an amino acid linker between any two regions depicted in the structures described herein. In some embodiments, the antigen-binding polypeptide complex can contain an Fc region, a CH1 region, a CL region, or any combination thereof. In some embodiments, the antigen-binding polypeptide complex is an antibody or an antigen-binding fragment thereof.

[0166] The antigen-binding polypeptides and antigen-binding polypeptide complexes described herein specifically bind to HIV proteins. This includes specific binding to one or more HIV proteins and specific binding to one or more epitopes on the same HIV protein. In some embodiments, the HIV protein is selected from the group consisting of an HIV envelope protein, an HIV structural protein, an HIV functional protein, or an HIV accessory protein. In some embodiments, the HIV envelope protein is an HIV envelope glycoprotein (Env), an HIV envelope glycoprotein gp160, an HIV envelope surface glycoprotein gp120, or an HIV transmembrane envelope protein gp41. In some embodiments, the HIV structural protein is p17, p24, p7, or p55. In some embodiments, the HIV functional protein is p66, HIV-1 protease (PR), or p31. In some embodiments, the HIV accessory protein is Nef, Tat, Rev, Vif, Vpr, or Vpu.

[0167] In some embodiments, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide has a structure represented by VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; or VH1-L1-VH2-L2-VL2-L3-VL1; the second polypeptide has a structure represented by VL3-VL4-VH4-VH3; VH3-VH4-VL4-VL3; VL3-L4-VL4-L5-VH4-L6-VH3; or VH3-L4-VH4-L5-VL4-L6-VL3; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL2 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0168] In another aspect, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; or VH1-L1-VH2-L2-VL2-L3- VL1-L4-Fc; the second polypeptide has a structure represented by VL3-VL4-VH4-VH3-Fc; VH3-VH4-VL4-VL3-Fc; VL3-L5-VL4-L6-VH4-L7-VH3-Fc; VH3-L5-VH4-L6-VL4-L7-VL3-Fc; VL3-L5-VL4-L6-VH4-L7-VH3-L8-Fc; or VH3-L5-VH4-L6-VL4-L7-VL3-L8-Fc; and VL1 is an HIV tandem VH1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, L6, L7, and L8 are amino acid linkers.

[0169] In another aspect, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-CH1; VH1-VH2-VL2-VL1-CH1; VL1-VL2-VH2-VH1-CL; VH1-VH2-VL2-VL1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CH1-CL; VH1-VH2-VL2-VL1-CH1-CL; VL1-VL2-VH2-VH1-CL-CH1; VH1-VH2-VL2-VL1-CL-CH1; VL1 -L1-VL2-L2-VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4 -CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1; the first polypeptide has a structure represented by VL3-VL4-VH4-VH3-CH1; VH3-VH4-VL4-VL3-CH1; VL3-VL4-VH4-VH3-CL; VH3-VH4-VL4-VL3-CL; VL3-VL4-VH4-VH3-CH1-CL; VH3-VH4-VL4-VL3-CH1-CL; VL3-VL4-VH4-VH3-CL-CH1; VH3-VH4-VL4-VL3-CL-CH1; VL3-VL4-VH4-VH3-CL-CH1; VH3-VH4-VL4-VL3-CL-CH1; VL3-L 6-VL4-L7-VH4-L8-VH3-L9-CH1;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CH1; VL3-L6-VL4-L7-VH4-L8-VH3-L9-CL;VH3-L6-VH4-L7-VL4-L8-VL3-L9-C L;VL3-L6-VL4-L7-VH4-L8-VH3-L9-CH1-L10-CL;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CH1-L10-CL;VL3-L6-VL4-L7-VH4-L8-VH3-L9-CL-L10-CH1;or having a structure represented by VH3-L6-VH4-L7-VL4-L8-VL3-L9-CL-L10-CH1; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; and VH1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, and L10 are amino acid linkers.

[0170] In another aspect, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide is VL1-VL2-VH2-VH1-CH1-Fc; VH1-VH2-VL2-VL1-CH1-Fc; VL1-VL2-VH2-VH1-CL-Fc; VH1-VH2-VL2-VL1-CL-Fc; VL1-VL2-VH2-VH1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-CH1-Fc; VL2-VL1-CL-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-F c;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc;VL or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-Fc; the second polypeptide has a structure represented by VL3-VL4-VH4-VH3-CH1-Fc; VH3-VH4-VL4-VL3-CH1-Fc; VL3-VL4-VH4-VH3-CL-Fc; VH3-VH4-VL4-VL3-CL-Fc; VL3-VL4-VH4-VH3-CH1-CL-Fc; VH3-VH4-VL4-VL3-CH 1-CL-Fc;VL3-VL4-VH4-VH3-CL-CH1-Fc;VH3-VH4-VL4-VL3-CL-CH1-Fc;VL3-L6-VL4-L7-VH4-L8-VH3-L9-CH1-Fc;VH3-L6-VH4-L7-VL4-L8-VL3- L9-CH1-Fc;VL3-L6-VL4-L7-VH4-L8-VH3-L9-CL-Fc;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CL-Fc;VL3-L6-VL4-L7-VH4-L8-VH3-L9-CH1-L10-CL-Fc;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CH1-L10-CL-Fc; VL3-L6-VL4-L7-VH4-L8-VH3-L9-CL-L10-CH1-Fc; or VH3-L6-VH4-L7-VL4-L8-VL3-L9-CL-L10-CH1-Fc; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; and VH1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, and L12 are amino acid linkers.

[0171] In another aspect, the present invention is directed to an antigen-binding polypeptide complex containing the 1st polypeptide and the 2nd polypeptide; the 1st polypeptide is VL1-VL2-VH2-VH1; -VL2-VL1-Fc;VL1-VL2-VH2-VH1-CH1;VH1-VH2-VL2-VL1-CH1;VL1-VL2-VH2-VH1-CL;VH1-VH2-VL2-VL1-CL;VL1-VL2-VH2-VH1-CH1-CL;VH1-VH2-V L2-VL1-CH1-CL;VL1-VL2-VH2-VH1-CL-CH1;VH1-VH2-VL2-VL1-CL-CH1;VL1-VL2-VH2-VH1-CH1-Fc;VH1-VH2-VL2-VL1-CH1-Fc;VL1-VL2-VH2-VH1-Fc CL-Fc;VH1-VH2-VL2-VL1-CL-Fc;VL1-VL2-VH2-VH1-CH1-CL-Fc;VH1-VH2-VL2-VL1-CH1-CL-Fc;VL1-VL2-VH2-VH1-CL-CH1-Fc;VH1-VH2-VL2-VL1-C L-CH1-Fc;VL1-L1-VL2-L2-VH2-L3-VH1;VH1-L1-VH2-L2-VL2-L3-VL1;VL1-L1-VL2-L2-VH2-L3-VH1-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-Fc;VL1-L1- VL2-L2-VH2-L3-VH1-L4-Fc;VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1;VL1- L1-VL2-L2-VH2-L3-VH1-L4-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL;VH1-L1-VH2-L2-VL2-L3-VL1-L 4-CH1-L5-CL;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1;VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1;VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc;Having a structure represented by VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-Fc; the second polypeptide is VL3-VL4-VH4-VH3; VH3-VH4-VL4-VL3; VL3-VL4-VH4-VH3-Fc; VH3-VH4-VL4-VL3-Fc; VL3-VL4-VH4-VH3-CH1; VH3-VH4-VL4-VL3-CH1; VL3-VL4-VH4-VH3-CL; VH3-VH4-VL4-VL3-CL; VL3-VL4-VH4-VH3-CH1-CL; VH3-VH4-VL4-VL3-CH1-CL; VL3-VL4-VH4-VH3-CL-CH1; VH3-VH4-VL4-VL3-CL-CH1; VL3-VL4-VH4-VH3-CH1-Fc; VH3-VH4-VL4-VL3-CH1-Fc; VL3-VL4-VH4-VH3-CL-Fc; VH3-VH4-VL4-VL3-CL-Fc; VL3-VL4-VH4-VH3-CH1-CL-Fc; VH3-VH4-VL4-VL3-CH1-CL-Fc; VL3-VL4-VH4-VH3-CL-CH1-Fc; VH3-VH4-VL4-VL3-CL-CH1-Fc; VL3-L6-VL4-L7-VH4-L8-VH3; VH3-L6-VH4-L7-VL4-L8-VL3; VL3-L6-VL4-L7-VH4-L8-VH3-Fc; VH3-L6-VH4-L7-VL4-L8-VL3-Fc; VL3-L6-VL4-L7-VH4-L8-VH3-L9-Fc; VH3-L6-VH4-L7-VL4-L8-VL3-L9-Fc; VL3-L6-VL4-L7-VH4-L8-VH3-L9-CH1; VH3-L6-VH4-L7-VL4-L8-VL3-L9-CH1; VL3-L6-VL4-L7-VH4-L8-VH3-L9-CL;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CL;VL3-L6-VL4-L7-VH4-L8-VH3-L9-CH1-L10-CL;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CH1-L10-CL;VL3-L6-VL4-L 7-VH4-L8-VH3-L9-CL-L10-CH1;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CL-L1 0-CH1;VL3-L6-VL4-L7-VH4-L8-VH3-L9-CH1-Fc;VH3-L6-VH4-L7-VL4-L8 -VL3-L9-CH1-Fc;VL3-L6-VL4-L7-VH4-L8-VH3-L9-CL-Fc;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CL-Fc;VL3-L6-VL4-L7-VH4-L8-VH3-L9-CH1-L10-CL -Fc;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CH1-L10-CL-Fc;VL3-L6-VL4-L7-V H4-L8-VH3-L9-CL-L10-CH1-Fc;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CL-L10 -CH1-Fc;VL3-L6-VL4-L7-VH4-L8-VH3-L9-CH1-L10-Fc;VH3-L6-VH4-L7 -VL4-L8-VL3-L9-CH1-L10-Fc;VL3-L6-VL4-L7-VH4-L8-VH3-L9-CL-L10- Fc;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CL-L10-Fc;VL3-L6-VL4-L7-VH4-L 8-VH3-L9-CH1-L10-CL-L11-Fc;VH3-L6-VH4-L7-VL4-L8-VL3-L9-CH1-L1 0-CL-L11-Fc; VL3-L6-VL4-L7-VH4-L8-VH3-L9-CL-L10-CH1-L11-Fc; or VH3-L6-VH4-L7-VL4-L8-VL3-L9-CL-L10-CH1-L11-Fc; wherein VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; and VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein;VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region that includes immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge, where CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, or L11 is an amino acid linker;

[0172] In some embodiments of the antigen-binding polypeptides or antigen-binding polypeptide complexes of the invention, VH1, VH2, VH3, and VH4 each comprise a heavy chain variable region derived from the PGT121 antibody, VRC01 antibody, 10E8v4 antibody, or PG16 antibody, or a variant thereof; and / or VL1, VL2, VL3, and VL4 each comprise a light chain variable region derived from the PGT121 antibody, VRC01 antibody, 10E8v4 antibody, or PG16 antibody, or a variant thereof.

[0173] In some embodiments, VH1, VH2, VH3, and VH4 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 20-23; and / or VL1, VL2, VL3, and VL4 each comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 24-27.

[0174] In some embodiments, VH1, VH2, VH3, and VH4 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention each have a CDR1 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 60, 63, 66, and 69; a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 61, 64, 67, and 70; and a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 62, 65, 68, and 71. and VL1, VL2, VL3, and VL4 each comprise a CDR1 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 72, 75, 78, and 81; a CDR2 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 73, 76, 79, and 82; and a CDR3 having an amino acid sequence that is at least 90% identical, at least 95% identical, or 100% identical to any one of SEQ ID NOs: 74, 77, 80, and 83.

[0175] Other General Aspects The antigen-binding polypeptides and antigen-binding polypeptide complexes described herein specifically bind to HIV proteins. This includes specific binding to one or more HIV proteins and specific binding to one or more epitopes on the same HIV protein. In some embodiments, the HIV protein is selected from the group consisting of an HIV envelope protein, an HIV structural protein, an HIV functional protein, or an HIV accessory protein. In some embodiments, the HIV envelope protein is an HIV envelope glycoprotein (Env), an HIV envelope glycoprotein gp160, an HIV envelope surface glycoprotein gp120, or an HIV transmembrane envelope protein gp41. In some embodiments, the HIV structural protein is p17, p24, p7, or p55. In some embodiments, the HIV functional protein is p66, HIV-1 protease (PR), or p31. In some embodiments, the HIV accessory protein is Nef, Tat, Rev, Vif, Vpr, or Vpu.

[0176] Antigen-binding sequences of HIV proteins (e.g., antibody CDR, VH, VL, heavy and light chain sequences) are well known. Such antibodies include, but are not limited to, PGT145, PG9, PG16, PGT128, PGT121, 10-1074, 3BNC117, VRC01, PGT151, 4E10, 10E8, or variants thereof (e.g., 10E8v4). In addition, molecular biology and recombinant DNA methods for generating, screening, and engineering antigen-binding complexes and antibodies containing such sequences are well known, see, e.g., Adair et al. Human Antibodies, 5(1-2):41-47, 1994; Kostelny et al., J. Immunol., 148(5):1547-1553(1992), Shiraiwa et al., Methods, 154:10-20, 2019; and Zola, “Monoclonal Antibodies: A Manual of Techniques,” 1987, 1 stEd., CRC Press; and Steinitz, Human Antibodies, 18(1-2):1-10, 2009.

[0177] In some embodiments, an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention does not specifically bind to an antigen associated with severe acute respiratory syndrome (SARS).

[0178] In some embodiments, one or more of VH1, VH2, VH3, VH4, VH5, and VH6 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention comprise an amino acid sequence encoded by a polynucleotide having at least 90% identity, at least 95% identity, or 100% identity to SEQ ID NO:28 or 29; and / or one or more of VL1, VL2, VL3, VL4, VL5, and VL6 of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention comprise an amino acid sequence encoded by a polynucleotide having at least 90% identity, at least 95% identity, or 100% identity to SEQ ID NO:30 or 31.

[0179] In some aspects, the invention is directed to antigen-binding polypeptides or antigen-binding polypeptide complexes (e.g., antibodies or antigen-binding fragments thereof) that comprise one or more amino acid sequences having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 32-47, 84, 86, 88, 90, 92, 94, 96, and 98.

[0180] In another aspect, the invention is directed to an antigen-binding polypeptide or antigen-binding polypeptide complex (e.g., an antibody or antigen-binding fragment thereof) that comprises one or more amino acid sequences encoded by a polynucleotide having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 48-59, 85, 87, 89, 91, 93, 95, 97, and 99.

[0181] In some embodiments, the antigen-binding polypeptide or antigen-binding polypeptide complex (e.g., an antibody or antigen-binding fragment thereof) comprises an immunoglobulin hinge. In some embodiments, the immunoglobulin hinge comprises an upper hinge region, a middle hinge region, a lower hinge region, or a combination thereof.

[0182] As used herein, an antigen-binding polypeptide, antigen-binding polypeptide complex (e.g., an antibody or antigen-binding fragment thereof), or a region or domain thereof "specifically binds" refers to the association of the antigen-binding domain with an epitope, where the binding involves a degree of complementarity between the antigen-binding domain and the epitope. Specific binding to an epitope occurs via the antigen-binding domain and is more readily apparent than binding to a random, unrelated epitope.

[0183] As used herein, "epitope" refers to a localized region of an antigen to which an antigen-binding polypeptide or antigen-binding polypeptide complex (e.g., an antibody or antigen-binding fragment thereof) can specifically bind. An epitope can be, for example, consecutive amino acids of a polypeptide (linear or consecutive epitope), or an epitope can be assembled, for example, from two or more non-contiguous regions of a polypeptide or multiple polypeptides (conformational, non-linear, non-contiguous or non-contiguous epitopes). In some embodiments, the epitope to which an antibody or antigen-binding fragment thereof binds can be determined, for example, by NMR spectroscopy, X-ray diffraction crystallography studies, ELISA assays, hydrogen / deuterium exchange coupled with mass spectrometry (e.g., liquid chromatography electrospray mass spectrometry), array-based oligopeptide scanning assays, and / or mutagenesis mapping (e.g., site-directed mutagenesis mapping).For example, Giege R et al.,(1994)Acta Crystallogr.D Biol.Crystallogr.50(Pt 4):339-350;McPherson A(1990)Eur. A(1976)J.Biol.Chem.251:6300-6303;Meth.Enzymol.(1985) volumes 114 & 115,eds Wyckoff HW et al.,USPub.No.2004 / 0014194),Bricogne G(1993)Acta Crystallogr.D Biol.Crystallogr.49(Pt 1):37-60,Bricogne G (1997) Meth. Enzymol. 276A:361-423, ed Carter CW, and Roversi et al., (2000) Acta Crystallogr. D Biol. Crystallogr. 56(Pt 10):1316-1323 (X-ray diffraction crystallography studies); and Champe et al., (1995) J. Biol. Chem. 270:1388-1394 and Cunningham BC & Wells JA (1989) Science 244:1081-1085 (mutagenesis mapping).

[0184] Specific binding can be expressed in terms of "binding affinity." Binding affinity refers to the inherent binding affinity that reflects a 1:1 interaction between members of a binding pair (e.g., an antigen-binding polypeptide or antigen-binding polypeptide complex and an antigen). Binding affinity is determined by the equilibrium dissociation constant (K D ) can be measured and / or expressed in a number of ways known in the art, including, but not limited to, K D is k off / k on It is calculated from the quotient of k on k refers to, for example, the binding rate constant of an antigen-binding polypeptide or antigen-binding polypeptide complex to an antigen, offrefers, for example, to the dissociation of an antigen-binding polypeptide or antigen-binding polypeptide complex from the antigen. on and k off can be determined by techniques known to those skilled in the art such as Octet BLI, BIAcore® or KinExA.

[0185] Thus, in some embodiments, the antigen-binding polypeptide complex of the present invention is an antibody or an antigen-binding fragment thereof. In some embodiments, the antibody or antigen-binding fragment thereof comprises one, two, or three antigen-binding polypeptides described herein. In some embodiments, the antibody or antigen-binding fragment thereof is bispecific, trispecific, tetraspecific, pentaspecific, or hexaspecific. In other embodiments, the antibody or antigen-binding fragment thereof is bivalent, trivalent, tetravalent, pentavalent, or hexavalent.

[0186] In some embodiments, the antibody or antigen-binding fragment thereof has an equilibrium dissociation constant (K D In some embodiments, the antibody is an IgG, an IgM, an IgE, an IgA, or an IgD. In some embodiments, the IgG is an IgG1, an IgG2, an IgG3, or an IgG4. In some embodiments, the antigen-binding fragment is a Fab, scFab, Fab', F(ab') 2 , Fv or scFv. In yet another embodiment, the antibody is a human antibody or a humanized antibody.

[0187] Amino Acid Linker In some embodiments, an antigen-binding polypeptide or antigen-binding polypeptide complex (e.g., an antibody or antigen-binding fragment thereof) of the invention comprises one or more amino acid linkers between one or more regions of the antigen-binding polypeptide or antigen-binding polypeptide complex.

[0188] As used herein, an "amino acid linker" refers to a single amino acid or a short amino acid sequence capable of linking two polypeptide regions of the invention described herein in a stable manner that maintains or enhances the function associated with the polypeptide regions. In some embodiments, amino acid linkers are represented herein by the abbreviation "l" or "L" and a number in the structure of an antigen-binding polypeptide or antigen-binding polypeptide complex (e.g., L1 meaning first linker, L2 meaning second linker, L3 meaning third linker, L4 meaning fourth linker, L5 meaning fifth linker, L6 meaning sixth linker, L7 meaning seventh linker, L8 meaning eighth linker, L9 meaning ninth linker, L10 meaning tenth linker, L11 meaning eleventh linker, L12 meaning twelfth linker, L13 meaning thirteenth linker, and so forth). In some aspects, such a recited amino acid linker (e.g., L1) can have the same or a different sequence as another recited amino acid linker (e.g., L2, etc.). Additionally, in other aspects, a recited amino acid linker present in one polypeptide (e.g., L1 on a first polypeptide of an antigen-binding polypeptide and / or antigen-binding polypeptide complex structure described herein) can have the same or a different sequence as the same recited amino acid linker present in another polypeptide (e.g., L1 on a second polypeptide, a third polypeptide, etc. of an antigen-binding polypeptide and / or antigen-binding polypeptide complex structure described herein).

[0189] In some embodiments, the amino acid linker (e.g., one or more of L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, etc., of the first, second, third, etc. polypeptide of the antigen-binding polypeptide or antigen-binding polypeptide complex structure described herein) has a length of about 1 amino acid to about 50 amino acids. In some embodiments, the amino acid linker has a length of about 1 amino acid to about 45 amino acids, about 1 amino acid to about 40 amino acids, about 1 amino acid to about 35 amino acids, about 1 amino acid to about 30 amino acids, about 1 amino acid to about 25 amino acids, about 1 amino acid to about 20 amino acids, 1 amino acid to about 15 amino acids, about 1 amino acid to about 10 amino acids, about 1 amino acid to about 5 amino acids, about 5 amino acids to about 50 amino acids, about 5 amino acids to about 45 amino acids, about 5 amino acids to about 40 amino acids, about 5 amino acids to about 35 amino acids, about 5 amino acids to about 30 amino acids, about 5 amino acids to about 25 amino acids, about 5 amino acids to about 20 amino acids, about 5 amino acids to about 15 amino acids, about 5 amino acids to about 10 amino acids, about 10 amino acids to about 50 amino acids, about 10 amino acids to about 45 amino acids, about 10 amino acids to about 40 amino acids, about 10 amino acids to about 35 amino acids, about 10 amino acids to about 30 amino acids, about 10 amino acids to about 25 amino acids, about 10 amino acids to about 20 amino acids, about 10 amino acids to about 15 amino acids , about 15 amino acids to about 50 amino acids, about 15 amino acids to about 45 amino acids, about 15 amino acids to about 40 amino acids, about 15 amino acids to about 35 amino acids, about 15 amino acids to about 30 amino acids, about 15 amino acids to about 25 amino acids, about 15 amino acids to about 20 amino acids, about 20 amino acids to about 50 amino acids, about 20 amino acids to about 45 amino acids, about 20 amino acids to about 40 amino acids, about 20 amino acids to about 35 amino acids, about 20 amino acids to about 30 amino acids, about 20 amino acids to about 25 The nucleic acid sequence may be any sequence of about 25 to about 50 amino acids, about 25 to about 45 amino acids, about 25 to about 40 amino acids, about 25 to about 35 amino acids, about 25 to about 30 amino acids, about 30 to about 50 amino acids, about 30 to about 45 amino acids, about 30 to about 40 amino acids, about 30 to about 35 amino acids, about 40 to about 50 amino acids, about 40 to about 45 amino acids, or about 45 to about 50 amino acids.

[0190] In some embodiments, the amino acid linker (e.g., one or more of L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, etc., of the first, second, third, etc. polypeptide of an antigen binding polypeptide structure described herein, or of an antigen binding polypeptide complex structure described herein) has about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 25, about 30, about 35, about 40, about 45, or about 50 amino acids.

[0191] In some embodiments, the amino acid linker (e.g., one or more of L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, etc., of the first, second, third, etc. polypeptide of an antigen binding polypeptide structure described herein, or of an antigen binding polypeptide complex structure described herein) is comprised of one or more amino acid residues. In some embodiments, the amino acid residues are selected from the group consisting of glycine, alanine, serine, threonine, cysteine, asparagine, glutamine, leucine, isoleucine, valine, proline, histidine, aspartic acid, glutamic acid, lysine, arginine, methionine, phenylalanine, tryptophan, and tyrosine.

[0192] In some embodiments, the amino acid linkers of the invention are non-immunogenic. In some embodiments, the non-immunogenic linkers consist of serine, glycine and / or alanine residues, or consist of serine and / or glycine residues. In some embodiments, the amino acid linkers of the invention do not contain a T cell epitope or a consensus T cell epitope.

[0193] In some embodiments, the amino acid linker (e.g., one or more of L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, etc., of the first, second, third, etc. polypeptide of an antigen binding polypeptide structure described herein, or of an antigen binding polypeptide complex structure described herein) is comprised of one or more residues of alanine, cysteine, glycine, isoleucine, leucine, methionine, phenylalanine, proline, tryptophan, tyrosine, or valine.

[0194] Amino acid linker sequences that can be used with the antigen-binding polypeptides and antigen-binding polypeptide complexes of the invention (e.g., antibodies or antigen-binding fragments thereof) are well known and can be incorporated into the antigen-binding polypeptides and antigen-binding polypeptide complexes of the invention using routine molecular biology and recombinant DNA techniques. See, e.g., Chen et al., Adv Drug Deliv Rev., 65(10):1357-1369, 2013; and Chichili et al., Protein Sci., 22(2):153-167, 2013.

[0195] In some embodiments, the amino acid linker (e.g., one or more of L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, etc., of the first, second, third, etc. polypeptide of an antigen-binding polypeptide or antigen-binding polypeptide complex structure described herein) is selected from the group consisting of g, a, gss, asg, ggssg, gssgs, gtvaa, asggs, astgg, asggsg, ggsggssgss, sggsgssggs, ggsggsgsgggsasgsg, ggsggsgsggggsasgsg, gggssggggsggsgsggs gs,ggggsggsgsggggsasgsg,gggssggsgsggsgsggsgs,sggssggsgsggsgsggsgssg,gsgssggggsggsgsggsgssg,ggggsgsggsgggssggggsggggsggggsggggsggggs , ggggsggggsggggsggggsggggsggggsggggsggggs, ggggsgsggsgggssggggsggggsggggsggggsggggssss, ggggsggsgggssggggsggggsggggsggggsggggssssgs The sequence is ggsgg, gsggsagsgsggggsasgsg, ggggs, or gsggsggsgsggggsasgsg (SEQ ID NOs: 1 to 19 and 100 to 107), or a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% identity to any one of SEQ ID NOs: 1 to 19 and 100 to 107.

[0196] In some embodiments of the antigen-binding polypeptides or antigen-binding polypeptide complexes of the invention, L1 comprises the amino acid sequence of ggssg (SEQ ID NO:1), or an amino acid sequence that has at least 90% identity or at least 95% identity to SEQ ID NO:1; L2 comprises the amino acid sequence of ggggsggsgsggggsasgsg (SEQ ID NO:12), or an amino acid sequence that has at least 90% identity or at least 95% identity to SEQ ID NO:12; L3 comprises the amino acid sequence of SEQ ID NO:1, or an amino acid sequence that has at least 90% identity or at least 95% identity to SEQ ID NO:1; and L4 comprises the amino acid sequence of asggsg (SEQ ID NO:6), or an amino acid sequence that has at least 90% identity or at least 95% identity to SEQ ID NO:6.

[0197] In some embodiments, the invention is directed to an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide; the first polypeptide has a structure represented by VL1-VL2-VH2-VH1; VH1-VH2-VL2-VL1; VL1-L1-VL2-L2-VH2-L3-VH1; or VH1-L1-VH2-L2-VL2-L3-VL1; and the second polypeptide has a structure represented by VL3-VL4-VH4-VH3; VH3-VH4-VL4-VL3; VL3-L4-VL4-L5-VH4-L6-VH3; or VH3 -L4-VH4-L5-VL4-L6-VL3; VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds to an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds to an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds to an HIV protein; and VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein. VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; L1, L2, L3, L4, L5, and L6 are amino acid linkers; L1 comprises an amino acid sequence of ggssg (SEQ ID NO:1), or an amino acid sequence having at least 90% identity or at least 95% identity to SEQ ID NO:1; L2 is ggg L3 comprises the amino acid sequence of SEQ ID NO:1 or an amino acid sequence that has at least 90% identity or at least 95% identity to SEQ ID NO:1; L4 comprises the amino acid sequence of asggsg (SEQ ID NO:6) or an amino acid sequence that has at least 90% identity or at least 95% identity to SEQ ID NO:6.

[0198] Detectable Labels and Drug Conjugates In some embodiments, an antigen-binding polypeptide or antigen-binding polypeptide complex (e.g., an antibody or antigen-binding fragment thereof) of the invention comprises one or more detectable labels. Antigen-binding polypeptides or antigen-binding polypeptide complexes (e.g., antibodies or antigen-binding fragments thereof) containing detectable labels are useful in therapeutic, diagnostic, imaging (e.g., radioimaging), or basic research applications.

[0199] In some embodiments, the detectable label is a radioactive label. Examples of radioactive labels include isotopes 3 H, 14 C. 32 P, 35 S, 36 Cl, 51 Cr, 57 Co, 58 Co, 59 Fe, 90 Y, 121 I, 124 I, 125 I, 131 I, 111 In, 117 Lu, 211 At, 198 Au, 67 Cu, 225 Ac, 213 Bi, 99 Tc, 186 Re and 89 These include, but are not limited to, Zr.

[0200] In some embodiments, the detectable label is a chemiluminescent label, a fluorescent label, an enzyme, biotin, or a combination thereof.

[0201] In some embodiments, the detectable label is a peptide tag.In some embodiments, the peptide tag is located at the N-terminus of the polypeptide or polypeptide complex.In some embodiments, the peptide tag is located at the C-terminus of the polypeptide or polypeptide complex.In some embodiments, the peptide tag is an affinity tag or a fusion tag.

[0202] In some embodiments, the detectable label is a polyhistidine tag, a polyarginine tag, glutathione-S-transferase (GST), maltose-binding protein (MBP), chitin-binding protein (CBP), Strep-tag, thioredoxin (TRX), poly(NANP), a FLAG tag, an ALFA tag, a V5 tag, a Myc tag, a hemagglutinin (HA) tag, a Spot tag, a T7 tag, a NE tag, or a green fluorescent protein (GFP), or a combination thereof. In some embodiments, the polyhistidine tag consists of about 4 to about 10 histidine residues. In some embodiments, the polyhistidine tag consists of about 4, about 5, about 6, about 7, about 8, about 9, or about 10 histidine residues.

[0203] Further examples of detectable labels and methods for introducing detectable labels into polypeptides are known and include routine chemical, molecular biology and recombinant DNA techniques. See, for example, Hnatowich et al., Science, 220(4597):613-615, 1983; Yao et al., Int. J. Mol. Sci., 17(2):194, 2016; Kimple et al., Curr. Protoc. Protein Sci., 73:Unit 9.9, 2013; Sambrook J, Fritsch EF. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press; Cold Spring Harbor, NY: 1989; Molecular Cell Biology, 4 th See U.S. 6, 2019. edition, Section, 3.5, Purifying, Detecting and Characterizing Proteins; and Mahmoodi et al., Cogent Biology, 5(1):DOI:10 / 1080 / 23312025.2019.1665406.

[0204] In other embodiments, an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention (e.g., an antibody or antigen-binding fragment thereof) is conjugated to an agent as an antibody-drug conjugate (ADC). The ADCs of the invention are useful in therapeutic, diagnostic, imaging (e.g., radioimaging), or basic research applications.

[0205] In some aspects, the antigen-binding polypeptides or antigen-binding polypeptide complexes of the invention (e.g., antibodies or antigen-binding fragments thereof) are linked to cytotoxic agents, immunomodulatory agents, imaging agents, or therapeutic proteins, usually via a linker. The linker may include a cleavable unit or may not be cleavable. Cleavable units include, for example, disulfide-containing linkers that are cleavable via disulfide exchange, acid-labile linkers that are cleavable at acidic pH, and linkers that are cleavable by hydrolases, esterases, peptidases, and glucoronidases (e.g., peptide linkers and glucoronide linkers). Non-cleavable linkers are believed to release the drug via the proteolytic antibody degradation mechanism.

[0206] Methods for making ADCs are known and include, but are not limited to, conjugation via thiols, amides, aldehydes, or azides, and other routine chemical, molecular biology, and recombinant DNA techniques. See, e.g., Yao et al., Int. J. Mol. Sci., 17(2):194, 2016; Sambrook J, Fritsch EF. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press; Cold Spring Harbor, NY: 1989; Molecular Cell Biology, 4 thedition, Section 3.5, Purifying, Detecting and Characterizing Proteins; and Mahmoodi et al., Cogent Biology, 5(1):DOI:10 / 1080 / 23312025.2019.1665406.

[0207] Modifications In some aspects, the present invention is directed to an antigen-binding polypeptide or antigen-binding polypeptide complex (eg, an antibody or antigen-binding fragment thereof) that comprises an effector function mutation or a half-life extending mutation.

[0208] Effector functions are an important part of the humoral immune response and form a link between innate and adaptive immunity. Most effector functions are induced through the Fc region of antibodies, which can interact with complement proteins and specific Fc receptors. As used herein, "effector function mutations" refer to changes in amino acid sequence, usually in the Fc region, that can enhance or reduce effector function, for example, increasing the binding affinity of Fc to a specific Fc receptor or increasing antibody-dependent cellular cytotoxicity (ADCC) activity.

[0209] The "half-life" of a pharma- ceutically active substance is the time it takes for the amount of the substance administered into the body to be reduced by half. A "half-life extending mutation" of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention refers to an amino acid sequence change, usually in the Fc region, that extends the half-life of the antigen-binding polypeptide or antigen-binding polypeptide complex (e.g., by increasing Fc receptor binding affinity, slowing the rate of dissociation of the Fc from the Fc receptor, and / or by increasing sialylation).

[0210] Examples of effector function mutations that enhance function include, but are not limited to, the following substitutions in the Fc region based on the EU numbering scheme: S298A / E333A / K334A, S239D / I332E, S239D / A330L / I332E, and G236A / S239D / I332E. Examples of effector function mutations that reduce function include, but are not limited to, the following substitutions in the Fc region based on the EU numbering scheme: N297A and L234A / L235A. Further examples of effector function mutations, half-life extension mutations, and methods of incorporating them into amino acid sequences are known and are described, for example, in Saunders, "Conceptual Approaches to Modulating Antibody Effector Functions and Circulation Half-Life," Front.Immunol.June, 7, 2019.

[0211] In some aspects, the present invention is directed to an antigen-binding polypeptide or antigen-binding polypeptide complex (e.g., an antibody or antigen-binding fragment thereof) that comprises one or more knobs-into-hole modifications.

[0212] As used herein, the term "knob-into-hole modification" refers to a genetic modification that directs pairing of two polypeptides to promote heterodimerization. In some embodiments, the modification introduces a protrusion (knob) into one polypeptide and a cavity (hole) into the other polypeptide at the interface where the two polypeptides interact. In some embodiments, knob-into-hole modifications can be created by introducing only hole modifications, e.g., by substituting an amino acid residue with a side chain that is smaller than the original amino acid residue (e.g., substituting one or more serine, threonine, valine, or alanine residues, or combinations thereof). In yet another embodiment, knob-into-hole modifications can be created by introducing only knob modifications, e.g., by substituting an amino acid residue with a side chain that is larger than the original amino acid residue (e.g., substituting one or more tryptophan or tyrosine residues, or combinations thereof).

[0213] In some embodiments, the knobs-into-hole modifications are present at the binding interface of two Fc regions, the binding interface of two CH2 regions, the binding interface of two CH3 regions, the binding interface of a CL region and a CH1 region, or the binding interface of a VH region and a VL region (see, e.g., U.S. Patent Publication No. 2007 / 0178552, International Publication No. WO 96 / 027011, International Publication No. WO 98 / 050431, and Zhu et al., Protein Science 6:781-788, 1987).

[0214] In some embodiments, the antigen-binding polypeptide or antigen-binding polypeptide complex comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more knob-into-hole modifications.

[0215] Knob-into-hole modifications are well known and can be incorporated into the antigen-binding polypeptides and antigen-binding polypeptide complexes of the invention using routine molecular biology and recombinant DNA techniques (see, e.g., U.S. Patent Publication No. 2003 / 0078385, International Patent Publication No. WO96 / 027011; Ridgway et al., Protein Eng., 9:617-621, 1996; and Merchant et al., Nat. Biotechnol., 16:677-681, 1998).

[0216] In some embodiments, the knob-into-hole modification is an amino acid substitution. As used herein, such substitutions are described according to the EU numbering scheme of Kabat, which corresponds to the Protein Data Bank (PDB) numbering.

[0217] In some embodiments, the knob-into-hole modification is a knob substitution of S354C and / or T366W based on the EU numbering scheme.

[0218] In some embodiments, the knob-into-hole modification is a hole substitution of Y349C, T366S, L368A, Y407V, L234A, L235A, P239A, M428L, N433S, M252Y, S254T, T256E, or any combination thereof based on the EU numbering scheme.

[0219] In some embodiments, the knob-into-hole modifications are hole substitutions of Y349C, T366S, L368A, and Y407V based on the EU numbering scheme. In some embodiments, the knob-into-hole modifications are hole substitutions of L234A, L235A, and P239A based on the EU numbering scheme. In some embodiments, the knob-into-hole modifications are hole substitutions of L234A and L235A based on the EU numbering scheme. In some embodiments, the knob-into-hole modifications are hole substitutions of M428L and N433S based on the EU numbering scheme. In some embodiments, the knob-into-hole modifications are hole substitutions of M252Y, S254T, and T256E based on the EU numbering scheme.

[0220] In some embodiments, the antigen-binding polypeptide complex is an IgG1 antibody or an IgG4 antibody and the knob-into-hole modifications are knob substitutions of S354C and T366W, and hole substitutions of Y349C, T366S, L368A, and Y407V.

[0221] In some embodiments, the antigen-binding polypeptide complex is an IgG1 antibody or an IgG4 antibody and the knob-into-hole modifications are L234A, L235A, and hole substitutions at P239A.

[0222] In some embodiments, the antigen-binding polypeptide complex is an IgG1 antibody or an IgG4 antibody and the knob-into-hole modifications are hole substitutions at L234A and L235A.

[0223] In some embodiments, the antigen-binding polypeptide complex is an IgG1 antibody or an IgG4 antibody and the knob-into-hole modifications are M428L and hole substitutions of N433S.

[0224] In some embodiments, the antigen-binding polypeptide complex is an IgG1 antibody or an IgG4 antibody and the knob-into-hole modifications are M252Y, S254T, and T256E hole substitutions.

[0225] Chimeric Antigen Receptor In some embodiments of the invention, antigen-binding polypeptides and antigen-binding polypeptide complexes can be used in chimeric antigen receptor (CAR) therapy. In some embodiments, the invention is directed to a CAR comprised of an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention. In some embodiments, a CAR of the invention comprises an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention and a transmembrane region. In some embodiments, a CAR of the invention comprises an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention, a transmembrane region and an intracellular region. In some embodiments, the intracellular region comprises a costimulatory region and / or an intracellular signaling region. In some embodiments, the intracellular region is a T cell activation domain. In yet another embodiment, an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention is linked to the transmembrane region by an immunoglobulin hinge.

[0226] Methods for producing polypeptides, polynucleotides, vectors, cells, and proteins In some aspects, the invention is directed to a polypeptide encoding an antigen-binding polypeptide or antigen-binding polypeptide complex (e.g., an antibody or antigen-binding fragment thereof) described herein.

[0227] In another aspect, the invention is directed to a polypeptide comprising an amino acid sequence of one or more of SEQ ID NOs: 32-47, 84, 86, 88, 90, 92, 94, 96, a...

Claims

1. An antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide, the first polypeptide is VL1-VL2-VH2-VH1-Fc; VH1-VH2-VL2-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; or VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc having a structure represented by: the second polypeptide is VL3-VL4-VH4-VH3-Fc; VH3-VH4-VL4-VL3-Fc; VL3-L5-VL4-L6-VH4-L7-VH3-Fc; VH3-L5-VH4-L6-VL4-L7-VL3-Fc; VL3-L5-VL4-L6-VH4-L7-VH3-L8-Fc; or VH3-L5-VH4-L6-VL4-L7-VL3-L8-Fc having a structure represented by: where: VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; and L1, L2, L3, L4, L5, L6, L7, and L8 are amino acid linkers; The antigen-binding polypeptide complex.

2. An antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide, the first polypeptide is VL1-VL2-VH2-VH1-CH1-Fc; VH1-VH2-VL2-VL1-CH1-Fc; VL1-VL2-VH2-VH1-CL-Fc; VH1-VH2-VL2-VL1-CL-Fc; VL1-VL2-VH2-VH1-CH1-CL-Fc; VH1-VH2-VL2-VL1-CH1-CL-Fc; VL1-VL2-VH2-VH1-CL-CH1-Fc; VH1-VH2-VL2-VL1-CL-CH1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CH1-L5-CL-L6-Fc; VH1-L1-VH2-L2-VL2-L3-VL1-L4-CH1-L5-CL-L6-Fc; VL1-L1-VL2-L2-VH2-L3-VH1-L4-CL-L5-CH1-L6-Fc; Or VH1-L1-VH2-L2-VL2-L3-VL1-L4-CL-L5-CH1-L6-Fc having a structure represented by; wherein the second polypeptide is VL3-VL4-VH4-VH3-CH1-Fc; VH3-VH4-VL4-VL3-CH1-Fc; VL3-VL4-VH4-VH3-CL-Fc; VH3-VH4-VL4-VL3-CL-Fc; VL3-VL4-VH4-VH3-CH1-CL-Fc; VH3-VH4-VL4-VL3-CH1-CL-Fc; VL3-VL4-VH4-VH3-CL-CH1-Fc; VH3-VH4-VL4-VL3-CL-CH1-Fc; VL3-L7-VL4-L8-VH4-L9-VH3-L10-CH1-Fc; VH3-L7-VH4-L8-VL4-L9-VL3-L10-CH1-Fc; VL3-L7-VL4-L8-VH4-L9-VH3-L10-CL-Fc; VH3-L7-VH4-L8-VL4-L9-VL3-L10-CL-Fc; VL3-L7-VL4-L8-VH4-L9-VH3-L10-CH1-L11-CL-Fc; VH3-L7-VH4-L8-VL4-L9-VL3-L10-CH1-L11-CL-Fc; VL3-L7-VL4-L8-VH4-L9-VH3-L10-CL-L11-CH1-Fc; VH3-L7-VH4-L8-VL4-L9-VL3-L10-CL-L11-CH1-Fc; VL3-L7-VL4-L8-VH4-L9-VH3-L10-CH1-L11-Fc; VH3-L7-VH4-L8-VL4-L9-VL3-L10-CH1-L11-Fc; VL3-L7-VL4-L8-VH4-L9-VH3-L10-CL-L11-Fc; VH3-L7-VH4-L8-VL4-L9-VL3-L10-CL-L11-Fc; VL3-L7-VL4-L8-VH4-L9-VH3-L10-CH1-L11-CL-L12-Fc; VH3-L7-VH4-L8-VL4-L9-VL3-L10-CH1-L11-CL-L12-Fc; VL3-L7-VL4-L8-VH4-L9-VH3-L10-CL-L11-CH1-L12-Fc; or VH3-L7-VH4-L8-VL4-L9-VL3-L10-CL-L11-CH1-L12-Fc having a structure represented by: where: VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is immunoglobulin heavy chain constant region 1; CL is an immunoglobulin light chain constant region; and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, and L12 are amino acid linkers; The antigen-binding polypeptide complex.

3. 3. The antigen-binding polypeptide complex of claim 1 or 2, wherein VH1, VH2, VH3, and VH4 specifically bind to different HIV proteins or to different epitopes on the same HIV protein.

4. 4. The antigen-binding polypeptide complex of claim 3, wherein VL1, VL2, VL3, and VL4 specifically bind to different HIV proteins or to different epitopes on the same HIV protein.

5. 3. The antigen-binding polypeptide complex of claim 1 or 2, wherein the HIV protein is an HIV envelope protein, an HIV structural protein, an HIV functional protein, or an HIV accessory protein.

6. The antigen-binding polypeptide complex of claim 5, wherein the HIV envelope protein is HIV envelope glycoprotein (Env), HIV envelope glycoprotein gp160, HIV envelope surface glycoprotein gp120, or HIV transmembrane envelope protein gp41.

7. The antigen-binding polypeptide complex of claim 5, wherein the HIV structural protein is p17, p24, p7, or p55.

8. The antigen-binding polypeptide complex of claim 5, wherein the HIV functional protein is p66, HIV-1 protease (PR), or p31.

9. The antigen-binding polypeptide complex of claim 5, wherein the HIV accessory protein is Nef, Tat, Rev, Vif, Vpr, or Vpu.

10. The antigen-binding polypeptide complex of claim 1 or 2, comprising VH and VL sequences derived from an N6 antibody, a PGT145 antibody, a PG9 antibody, a PG16 antibody, a PGT128 antibody, a PGT121 antibody, a 10-1074 antibody, a 3BNC117 antibody, a VRC01 antibody, a PGT151 antibody, a 4E10 antibody, or a 10E8 antibody, or a variant thereof.

11. The antigen-binding polypeptide complex of claim 10, comprising VH and VL sequences derived from the PGT121 antibody or a variant thereof.

12. The antigen-binding polypeptide complex of claim 10, comprising VH and VL sequences derived from the VRC01 antibody or a variant thereof.

13. The antigen-binding polypeptide complex of claim 10, wherein the variant of the 10E8 antibody is the 10E8v4 antibody.

14. The antigen-binding polypeptide complex of claim 1 or 2, wherein VH1, VH2, VH3, and VH4 each comprise a heavy chain variable region derived from a PGT121 antibody, a VRC01 antibody, a 10E8v4 antibody, or a PG16 antibody, or a variant thereof; and / or VL1, VL2, VL3, and VL4 each comprise a light chain variable region derived from a PGT121 antibody, a VRC01 antibody, a 10E8v4 antibody, or a PG16 antibody, or a variant thereof.

15. The antigen-binding polypeptide complex of claim 14, wherein VH1, VH2, VH3, and VH4 each comprise a heavy chain variable region derived from the PGT121 antibody or a variant thereof; and / or VL1, VL2, VL3, and VL4 each comprise a light chain variable region derived from the PGT121 antibody or a variant thereof.

16. The antigen-binding polypeptide complex of claim 14, wherein VH1, VH2, VH3, and VH4 each comprise a heavy chain variable region derived from the VRC01 antibody or a variant thereof; and / or VL1, VL2, VL3, and VL4 each comprise a light chain variable region derived from the VRC01 antibody or a variant thereof. Claim 17: VH1, VH2, VH3, and VH4 each comprise: CDR1 having an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 60, 63, 66, and 69; CDR2 having an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 61, 64, 67, and 70; and CDR3 having an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 62, 65, 68, and 71; and 3, and VL4 each comprise: CDR1 having an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 72, 75, 78, and 81; CDR2 having an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 73, 76, 79, and 82; and CDR3 having an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 74, 77, 80, and 83.

18. 3. The antigen-binding polypeptide complex of claim 1 or 2, wherein one or more of VH1, VH2, VH3, and VH4 comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 20-23.

19. 19. The antigen-binding polypeptide complex of claim 18, wherein one or more of VL1, VL2, VL3, and VL4 comprise an amino acid sequence having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs:24-27.

20. 3. The antigen-binding polypeptide complex of claim 1 or 2, wherein the immunoglobulin hinge comprises an upper hinge region, a middle hinge region, a lower hinge region, or a combination thereof.

21. 3. The antigen-binding polypeptide complex of claim 1 or 2, wherein linkers L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, and / or L12 have a length of from about 1 amino acid to about 50 amino acids.

22. The linkers L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, and / or L12 are g, a, gss, asg, ggssg, gssgs, gtvaa, asggs, astgg, asggsg, ggsggssgss, sggsgssggs, ggsggsgsgggsasgsg, ggsggsgsggggsasgsg, gggs sggggsggsgsggsgs, ggggsggsgsgsggggsasgsg, gggssggsgsggsgsggsgs, sgggssggsgsgsggsgsggsgsssg , gsgssggggsggsgsgsggsgsssg, ggggsgsggsggggssggggsggggsggggsggggsggggs, ggggsggggsggggsg ggggsggggsggggsggggsggggs, ggggsgsggsggggssggggsggggsggggsggggsggggssss, ggggsgsgsggsgg gssggggsggggsggggsggggsggggsssssgs, ggsgg, gsggsagsgsggggsasgsg, ggggs, and gsggsggsgsgs 3. The antigen-binding polypeptide complex of claim 1 or 2, comprising the amino acid sequence of ggsasgsg (SEQ ID NOS: 1-19 and 100-107), or a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% identity to any one of SEQ ID NOS: 1-19 and 100-107.

23. The antigen-binding polypeptide complex of claim 1 or 2, wherein the amino acid linker is non-immunogenic.

24. 3. The antigen-binding polypeptide complex of claim 1 or 2, wherein the Fc region comprises at least one knob-into-hole modification.

25. the antigen-binding polypeptide complex is an IgG1 antibody or an IgG4 antibody, and the knob-into-hole modification is based on the EU numbering scheme. (i) knob substitutions of S354C and T366W and hole substitutions of Y349C, T366S, L368A, and Y407V; (ii) hole substitutions at L234A, L235A, and P239A; (iii) hole substitutions at L234A and L235A; (iv) M428L and N433S hole substitutions; (v) M252Y, S254T, and T256E hole substitutions; or (vi) combinations thereof 25. The antigen-binding polypeptide complex of claim 24, comprising:

26. 3. The antigen-binding polypeptide complex of claim 1 or 2, comprising a detectable label.

27. 27. The antigen-binding polypeptide complex of claim 26, wherein the detectable label is a radioactive label, a chemiluminescent label, a fluorescent label, an enzyme, or a peptide tag, or a combination thereof.

28. 28. The antigen-binding polypeptide complex of claim 27, wherein the peptide tag is a polyhistidine tag consisting of about 4 to about 10 histidine residues.

29. 29. The antigen-binding polypeptide complex of claim 28, wherein the polyhistidine tag consists of approximately 8 histidine residues.

30. 3. The antigen-binding polypeptide complex of claim 1 or 2, which is conjugated to an active agent as an antibody-drug conjugate (ADC).

31. 31. The antigen-binding polypeptide complex of claim 30, wherein the agent is a cytotoxic agent, an immunomodulatory agent, an imaging agent, or a therapeutic protein, or a combination thereof.

32. 3. The antigen-binding polypeptide complex of claim 1 or 2, which binds to an HIV protein with an equilibrium dissociation constant (KD) of about 10 μM to about 1 pM.

33. An antibody or antigen-binding fragment thereof comprising an antigen-binding polypeptide complex according to claim 1 or 2.

34. 34. The antibody or antigen-binding fragment thereof of claim 33, wherein the antibody is IgG, IgM, IgE, IgA, or IgD.

35. The antibody or antigen-binding fragment thereof of claim 34, wherein the IgG is IgG1, IgG2, IgG3, or IgG4.

36. The antibody or antigen-binding fragment thereof of claim 33, wherein the antigen-binding fragment is a Fab, scFab, Fab', F(ab')2, Fv, or scFv.

37. 34. The antibody or antigen-binding fragment thereof of claim 33, wherein the antibody is a human antibody or a humanized antibody.

38. A polypeptide having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 32-47, 84, 86, 88, 90, 92, 94, 96, and 98.

39. A polynucleotide having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 48-59, 85, 87, 89, 91, 93, 95, 97, and 99.

40. A vector comprising the polynucleotide of claim 39.

41. A host cell comprising the vector of claim 40.

42. A chimeric antigen receptor (CAR) comprising the antigen-binding polypeptide complex of claim 1 or 2.

43. An immune cell comprising the CAR of claim 42.

44. A pharmaceutical composition comprising (i) an antigen-binding polypeptide complex according to claim 1 or 2, and (ii) a pharmaceutically acceptable carrier.

45. A kit comprising an antigen-binding polypeptide complex according to claim 1 or 2.

46. ​​A pharmaceutical composition for treating or preventing human immunodeficiency virus (HIV) infection, comprising the antigen-binding polypeptide complex of claim 1 or 2.

47. 47. The pharmaceutical composition of claim 46, wherein the HIV is HIV-1.

48. A pharmaceutical composition for treating or preventing acquired immune deficiency syndrome (AIDS), comprising the antigen-binding polypeptide complex of claim 1 or 2.

49. A pharmaceutical composition for treating or preventing AIDS-related complex (ARC), comprising the antigen-binding polypeptide complex of claim 1 or 2.

50. A pharmaceutical composition for treating or preventing an HIV-associated opportunistic infection, comprising an antigen-binding polypeptide complex according to claim 1 or 2.

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