HIV-targeting multispecific antigen-binding molecule and method of use

Abstract

To provide a multispecific antigen-binding molecule targeting HIV and a method for its use. [Solution] A multispecific antigen-binding molecule is provided, comprising a bispecific antibody that binds to CD3 containing the HIV envelope protein gp120 and to the HIV antigen. Methods of using such an antigen-binding molecule to treat or prevent HIV infection are also provided. In some embodiments, the multispecific or bispecific molecule comprises a first antigen-binding domain targeting human CD3, which is a single-chain variable fragment (scFv) fused to Fc, while a second antigen-binding domain targeting the HIV antigen (e.g., gp120 or gp41) consists of a Fab antigen-binding fragment fused to Fc.

Description

[Technical Field]

[0001] Cross-reference of related applications This application asserts the interests of U.S. Provisional Application No. 63 / 070,141, filed on 25 August 2020, and U.S. Provisional Application No. 63 / 163,713, filed on 19 March 2021, pursuant to 35 United States Code, which are incorporated herein by reference in their entirety for all purposes.

[0002] A multispecific antigen-binding molecule and its antigen-binding fragment are provided for the treatment and / or prevention of human immunodeficiency virus (HIV) infection.

[0003] Sequence List This application includes an electronically submitted sequence listing in ASCII format, the entirety of which is incorporated herein by reference. The ASCII copy, created on June 25, 2021, is named 1337-WO-PCT_SL.txt and has a size of 1,167,237 bytes. [Background technology]

[0004] Human immunodeficiency virus (HIV) infection and related diseases are a major public health problem worldwide. Most currently approved therapies for HIV infection target viral reverse transcriptase, protease, and integrase. However, HIV resistance to these existing drugs, long-term toxicity, and lack of patient adherence to daily dosing regimens are associated with these therapies. Therefore, it is crucial to discover and develop novel anti-HIV antibodies with advantageous properties suitable for therapeutic use.

[0005] International Publications 2005 / 058963, 2010 / 107939, 2012 / 030904, 2012 / 158948, 2013 / 090644, 2013 / 016468, 2013 / 192589, 2014 / 063059, and 2018 / 125813 describe human anti-HIV antibodies derived from memory B cells of HIV-infected donors that can inhibit infection by HIV-1 species from multiple clades. However, the therapeutic use of antibodies is limited by their in-patient viral coverage, pharmacokinetics, induction of anti-drug antibodies, off-target binding (i.e., polyspecificity), and other properties that hinder efficient manufacturing and storage.

[0006] A multispecific antigen-binding molecule is a single molecule capable of binding to at least two different antigens. A bispecific antigen-binding molecule is a single molecule capable of binding to two different antigens. This property can be utilized in several ways to improve the potency and / or selectivity of biotherapeutic drugs, for example, by generating novel functions (e.g., emicizumab mimicking factor VIII) by neutralizing the activity of two disease mediators instead of one, by enhancing selective binding to disease compared to normal tissue, or by directly recruiting immune cells for targeted death (e.g., blinatumomab recruitment of CD3+ T cells to kill CD19+ B cells). Thus, the field of bispecific antibodies is growing rapidly and has potential applications in almost every therapeutic area. Currently, there are three approved bispecific products (blinatumomab, ebumicizumab, and catumakisomab) and more than 50 clinical trials are underway (antibodysociety.org).

[0007] Numerous different bispecific antibody formats have been described, many of which are used to develop therapeutic molecules (e.g., outlined in Spiess and Carter, 2015, Mol. Immunol, 67:95-106). The production of bispecific antibodies is typically more complex than that of conventional antibodies. For example, Genmab... Fab arm replacement bispecifics such as the Duobody platform (Labrijn et.al., 2013, PNAS, 110:5145-5150) The generation of the desired bispecific molecule requires the separate production of each half-antibody (as IgG), followed by mixing them together under special conditions that allow for Fab arm exchange of the two half-antibodies to produce the desired bispecific molecule. The need for separate cell lines to produce each half-antibody (or unreacted parental reductate) IgG, the purification of these intermediates, and the optimization of the Fab arm exchange reaction and process for purifying the target bispecificity from residual half-antibody IgG add significant time and complexity to the research and development. Other bispecificity format strategies, such as those involving the pairing of an scFv fusion protein with a Fab-Fc fusion protein (e.g., International Publication 2016 / 086196, International Publication 2016 / 071004), ensure that only a single light chain is present as a strategy to avoid Fab arm exchange. Challenges arise in bispecificity formats involving scFv because the scFv portion can often not bind to the target antigen with the desired affinity, may have undesirable off-target binding, may not be sufficiently expressed, may be difficult to purify, and may contribute to bispecific molecules that do not have a sufficient serum half-life to enable efficacy for the intended indication. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] International Publication No. 2005 / 058963 [Patent Document 2] International Publication No. 2010 / 107939 [Patent Document 3] International Publication No. 2012 / 030904 [Patent Document 4] International Publication No. 2012 / 158948 [Patent Document 5] International Publication No. 2013 / 090644 [Patent Document 6] International Publication No. 2013 / 016468 [Patent Document 7] International Publication No. 2013 / 192589 [Patent Document 8] International Publication No. 2014 / 063059 [Patent Document 9] International Publication No. 2018 / 125813 [Non-patent literature]

[0009] [Non-Patent Document 1] Spiess and Carter,2015,Mol.Immunol,67:95-106 [Non-Patent Document 2] Genmab Duobody platform (Labrijn et.al., 2013, PNAS, 110:5145-5150) [Overview of the project] [Means for solving the problem]

[0010] In one embodiment, a multispecific (e.g., bispecific) antigen-binding molecule that binds to human CD3 and HIV antigen is provided. In some embodiments, a multispecific (e.g., bispecific) antigen-binding molecule comprises (a) a first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), wherein the first antigen-binding domain binds to CD3 and (i) a first VH complementarity determining region comprising the amino acid TYAMN (SEQ ID NO: 1). (ii) First VH-CDR2 containing the amino acid sequence RIRSKYNNYATYYAX1SVKX2 (wherein X1 is A or D, and X2 is G or S) (SEQ ID NO: 2), (iii) First VH-CDR3 containing the amino acid sequence HGNFGX3SYVSWFAY (wherein X3 is H or N) (SEQ ID NO: 3), (iv) First VL-CDR1 containing the amino acid sequence GSSTGAVTTGHYAN (SEQ ID NO: 4), (v) GTX4X5RAP (wherein X4X (5) comprises a first VL-CDR2 comprising the amino acid sequence of (SEQ ID NO: 5) (SN or NK), and (vi) a first VL-CDR3 comprising the amino acid sequence of (SEQ ID NO: 6) (ALWYSNX6WV) (where X6 is L or R), wherein the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VH-CDR3 each comprise a first antigen-binding domain according to Kabat, and (b) a second antigen-binding domain that binds to the HIV antigen.In some embodiments, the antigen-binding molecule is a multispecific (e.g., bispecific) antigen-binding molecule that binds to human CD3 and a second antigen, the antigen-binding molecule comprising: (a) a first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), wherein the first antigen-binding domain binds to CD3 and comprises: (i) a first VH complementarity-determining region (CDR) 1 comprising the amino acid TYAMN (SEQ ID NO: 1), (ii) a first VH-CDR2 comprising the amino acid sequence RIRSKYNNYATYYAX1SVKX2 (wherein X1 is A or D and X2 is G or S) (SEQ ID NO: 2), and (iii) the amino acid HGNFGX3SYVSWFAY (wherein X3 is H or N) (SEQ ID NO: 3). (iv) A first VL-CDR1 containing the amino acid sequence of (v) GSSTGAVTTGHYAN (SEQ ID NO: 4), a first VL-CDR2 containing the amino acid sequence of (v) GTX4X5RAP (wherein X4X5 is SN or NK) (SEQ ID NO: 5), and (vi) A first VL-CDR3 containing the amino acid sequence of ALWYSNX6WV (wherein X6 is L or R) (SEQ ID NO: 6), wherein the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VH-CDR3 each contain a first antigen-binding domain according to Kabat, and (b) a second antigen-binding domain that binds to a second antigen. In some embodiments, (i) the first VH complementarity-determining region (CDR) 1 comprises the amino acid sequence of TYAMN (SEQ ID NO: 1), (ii) the first VH-CDR2 comprises the amino acid sequence of RIRSKYNNYATYYADSVKX2 (where X2 is G or S) (SEQ ID NO: 7), (iii) the first VH-CDR3 comprises the amino acid sequence of HGNFGHSYVSWFAY (SEQ ID NO: 8), (iv) the first VL-CDR1 comprises the amino acid sequence of GSSTGAVTTGHYAN (SEQ ID NO: 4), (v) the first VL-CDR2 comprises the amino acid sequence of GTSNRAP (SEQ ID NO: 9), and (vi) the first VL-CDR3 comprises the amino acid sequence of ALWYSNRWV (SEQ ID NO: 10).In some embodiments, the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each include the following amino acid sequences (according to Kabat): (i) SEQ ID NOs: 1, 11, 8, 4, 5, and 10; (ii) SEQ ID NOs: 1, 11, 8, 4, 9, and 10; (iii) SEQ ID NOs: 1, 12, 8, 4, 9, and 10; (iv) SEQ ID NOs: 1, 13, 8, 4, 14, and 15, (v) SEQ ID NOs: 1, 13, 16, 4, 14, and 15; or (vi) SEQ ID NOs: 1, 11, 8, 4, 14, and 10. In some embodiments, the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VL-CDR3 each include the following amino acid sequences (according to Kabat): (i) SEQ ID NOs: 1, 11, 8, 4, 9, and 10, or (ii) SEQ ID NOs: 1, 12, 8, 4, 9, and 10. In some embodiments, the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VL-CDR3 each include the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 11, 8, 4, 9, and 10. In some embodiments, the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VL-CDR3 each include the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 12, 8, 4, 9, and 10.

[0011] In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises: (a) a first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), wherein the first antigen-binding domain binds to CD3 and comprises: (i) a first VH-CDR1 comprising the amino acid sequence GFTFNTY (SEQ ID NO: 17); (ii) a first VH-CDR2 comprising the amino acid sequence SKYNNY (SEQ ID NO: 18); (iii) a first VH-CDR3 comprising the amino acid sequence GNFGX3SYVSWFA (wherein X3 is H or N) (SEQ ID NO: 19); and (iv) SSTGAVTTGH (v) A first VL-CDR1 comprising the amino acid sequence Y (SEQ ID NO: 20), a first VL-CDR2 comprising the amino acid sequence GTX4 (wherein X4 is N or S) (SEQ ID NO: 21), and a first VL-CDR3 comprising the amino acid sequence WYSNX6W (wherein X6 is L or R) (SEQ ID NO: 22), wherein the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VH-CDR3 each comprise a first antigen-binding domain that follows Chothia, and (b) a second antigen-binding domain that binds to the HIV antigen.In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises: (a) a first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), wherein the first antigen-binding domain binds to CD3 and comprises: (i) a first VH-CDR1 comprising the amino acid sequence GFTFNTY (SEQ ID NO: 17); (ii) a first VH-CDR2 comprising the amino acid sequence SKYNNY (SEQ ID NO: 18); (iii) a first VH-CDR3 comprising the amino acid sequence GNFGX3SYVSWFA (wherein X3 is H or N) (SEQ ID NO: 19); and (iv) SSTGAVTTGH (v) A first VL-CDR1 comprising the amino acid sequence Y (SEQ ID NO: 20), a first VL-CDR2 comprising the amino acid sequence GTX4 (wherein X4 is N or S) (SEQ ID NO: 21), and a first VL-CDR3 comprising the amino acid sequence WYSNX6W (wherein X6 is L or R) (SEQ ID NO: 22), wherein the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VH-CDR3 each comprise a first antigen-binding domain that follows Chothia, and (b) a second antigen-binding domain that binds to a second antigen. In some embodiments, the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each include the following amino acid sequences (according to Chothia): (i) SEQ ID NOs: 17, 18, 23, 20, 21, and 25; (ii) SEQ ID NOs: 17, 18, 23, 20, 24, and 25; (iii) SEQ ID NOs: 17, 18, 23, 20, 26, and 27; (iv) SEQ ID NOs: 17, 18, 75, 20, 26, and 27; or (v) SEQ ID NOs: 17, 18, 23, 20, 26, and 25. In some embodiments, the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VL-CDR3 each include the following amino acid sequences (according to Chothia): SEQ ID NOs. 17, 18, 23, 20, 24, and 25.

[0012] In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises: (a) a first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), wherein the first antigen-binding domain binds to CD3 and comprises: (i) a first VH-CDR1 containing the amino acid sequence GFTFNTYA (SEQ ID NO: 28); (ii) a first VH-CDR2 containing the amino acid sequence IRSKYNNYAT (SEQ ID NO: 29); (iii) a first VH-CDR3 containing the amino acid sequence VRHGNFGX3SYVSWFAY (wherein X3 is H or N) (SEQ ID NO: 30); and (iv) TGAV The first VL-CDR1 comprises the amino acid sequence of TTGHY (SEQ ID NO: 31), the first VL-CDR2 comprises the amino acid sequence of (v)GTX4 (wherein X4 is N or S) (SEQ ID NO: 21), and the first VL-CDR3 comprises the amino acid sequence of (vi)ALWYSNX6WV (wherein X6 is L or R) (SEQ ID NO: 6), and the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VH-CDR3 each comprises a first antigen-binding domain according to IMGT and (b) a second antigen-binding domain that binds to the HIV antigen.In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises: (a) a first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), wherein the first antigen-binding domain binds to CD3 and comprises: (i) a first VH-CDR1 containing the amino acid sequence GFTFNTYA (SEQ ID NO: 28); (ii) a first VH-CDR2 containing the amino acid sequence IRSKYNNYAT (SEQ ID NO: 29); (iii) a first VH-CDR3 containing the amino acid sequence VRHGNFGX3SYVSWFAY (wherein X3 is H or N) (SEQ ID NO: 30); and (iv) TGAV (v) A first VL-CDR1 comprising the amino acid sequence of TTGHY (SEQ ID NO: 31), a first VL-CDR2 comprising the amino acid sequence of (v) GTX4 (wherein X4 is N or S) (SEQ ID NO: 21), and a first VL-CDR3 comprising the amino acid sequence of (vi) ALWYSNX6WV (wherein X6 is L or R) (SEQ ID NO: 6), wherein the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VH-CDR3 each comprise a first antigen-binding domain according to IMGT, and (b) a second antigen-binding domain that binds to a second antigen. In some embodiments, the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each include the following amino acid sequences (according to IMGT): (i) SEQ ID NOs. 28, 29, 32, 31, 21, and 10; (ii) SEQ ID NOs. 28, 29, 32, 31, 24, and 10; (iii) SEQ ID NOs. 28, 29, 32, 31, 26, and 15; (iv) SEQ ID NOs. 28, 29, 33, 31, 26, and 15; or (v) SEQ ID NOs. 28, 29, 32, 31, 26, and 10. In some embodiments, the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VL-CDR3 each include the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10.

[0013] In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises: (a) a first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), wherein the first antigen-binding domain binds to CD3 and comprises: (i) a first VH-CDR1 comprising the amino acid sequence ASGFTFNTYA (SEQ ID NO: 34); (ii) a first VH-CDR2 comprising the amino acid sequence IRSKYNNYATYYAX1SVKX2R (wherein X1 is A or D, and X2 is G or S) (SEQ ID NO: 35); (iii) a first VH-CDR3 comprising the amino acid sequence HGNFGX3SYVSWFA (wherein X3 is H or N) (SEQ ID NO: 36); and (iv) The first VL-CDR1 comprises the amino acid sequence SSTGAVTTGHY (SEQ ID NO: 37), the first VL-CDR2 comprises the amino acid sequence (v)GTX4NRAPX7VPAR (wherein X4 is N or S and X7 is G or W) (SEQ ID NO: 38), and the first VL-CDR3 comprises the amino acid sequence (vi)WYSNX6W (wherein X6 is L or R) (SEQ ID NO: 22), and the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VH-CDR3 each comprises a first antigen-binding domain that follows Honegger and (b) a second antigen-binding domain that binds to the HIV antigen.In some embodiments, a multispecific (e.g., bispecific) antigen-binding molecule comprises: (a) a first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), wherein the first antigen-binding domain binds to CD3 and comprises: (i) a first VH-CDR1 containing the amino acid ASGFTFNTYA (SEQ ID NO: 34); (ii) a first VH-CDR2 containing the amino acid sequence IRSKYNNYATYYAX1SVKX2R (wherein X1 is A or D, and X2 is G or S) (SEQ ID NO: 35); (iii) a first VH-CDR3 containing the amino acid sequence HGNFGX3SYVSWFA (wherein X3 is H or N) (SEQ ID NO: 36); and (iv) S (v) A first VL-CDR1 comprising the amino acid sequence STGAVTTGHY (SEQ ID NO: 37), a first VL-CDR2 comprising the amino acid sequence GTX4NRAPX7VPAR (wherein X4 is N or S, and X7 is G or W) (SEQ ID NO: 38), and a first VL-CDR3 comprising the amino acid sequence WYSNX6W (wherein X6 is L or R) (SEQ ID NO: 22), wherein the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VH-CDR3 each comprise a first antigen-binding domain that follows Honegger, and (b) a second antigen-binding domain that binds to a second antigen. In some embodiments, (i) the first VH-CDR1 comprises the amino acid sequence ASGFTFNTYA (SEQ ID NO: 34), (ii) the first VH-CDR2 comprises the amino acid sequence IRSKYNNYATYYADSVKX2R (where X2 is G or S) (SEQ ID NO: 39), (iii) the first VH-CDR3 comprises the amino acid sequence HGNFGHSYVSWFA (SEQ ID NO: 40), (iv) the first VL-CDR1 comprises the amino acid sequence SSTGAVTTGHY (SEQ ID NO: 37), (v) the first VL-CDR2 comprises the amino acid sequence GTSNRAPGVPAR (SEQ ID NO: 41), and (vi) the first VL-CDR3 comprises the amino acid sequence WYSNRW (SEQ ID NO: 25).In some embodiments, the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each include the following amino acid sequences (according to Honegger): (i) SEQ ID NOs: 34, 39, 40, 37, 41, and 25; (ii) SEQ ID NOs: 34, 42, 40, 37, 41, and 25; (iii) SEQ ID NOs: 34, 43, 40, 37, 41, and 25; (iv) SEQ ID NOs: 34, 44, 40, 37, 45, and 27; (v) SEQ ID NOs: 34, 44, 46, 37, 45, and 27; or (vi) SEQ ID NOs: 34, 42, 40, 37, 47, and 25. In some embodiments, the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VL-CDR3 each include the following amino acid sequences (according to Honegger): (i) SEQ ID NOs: 34, 42, 40, 37, 41, and 25, or (ii) SEQ ID NOs: 34, 43, 40, 37, 41, and 25. In some embodiments, the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VL-CDR3 each include the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 42, 40, 37, 41, and 25. In some embodiments, the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VL-CDR3 each include the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 42, 40, 37, 41, and 25. In some embodiments, the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VL-CDR3 each include the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 43, 40, 37, 41, and 25. In some embodiments, the first VH-CDR1, first VH-CDR2, first VH-CDR3, first VL-CDR1, first VL-CDR2, and first VL-CDR3 each contain the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 43, 40, 37, 41, and 25.

[0014] With regard to further embodiments of the first antigen-binding domain of a multispecific (e.g., bispecific) antigen-binding molecule that targets or binds to CD3, in some embodiments the multispecific (e.g., bispecific) antigen-binding molecule comprises one or more of the following amino acid substitutions (numbering according to Kabat): position 81 of the first VH is Q or E, position 83 of the first VH is K or R, position 89 of the first VH is M or V, position 100 of the first VH is H, position 57 of the first VL is G or W, and / or position 75 of the first VL is I or L. In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule includes one or more of the following amino acid substitutions (numbering according to Kabat): (i) position 81 of the first VH is Q or E, (ii) position 83 of the first VH is R, (iii) position 89 of the first VH is V, (iv) position 100 of the first VH is H, (v) position 57 of the first VL is G, and / or (vi) position 75 of the first VL is I. In some embodiments, position 81 of the first VH (numbering according to Kabat) is E. In some embodiments, position 81 of the first VH (numbering according to Kabat) is Q. In some embodiments, position 100 of the first VH (numbering according to Kabat) is H. In some embodiments, the first VH includes an amino acid sequence selected from the group consisting of SEQ ID NOs. 48 to 53, or includes an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs. 48 to 53. In some embodiments, the first VH includes an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence of SEQ ID NOs. 50. In some embodiments, the first VH includes the amino acid sequence of SEQ ID NOs.In some embodiments, the first VH includes an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 51. In some embodiments, the first VH includes the amino acid sequence of SEQ ID NO: 51. In some embodiments, the first VL includes an amino acid sequence selected from the group consisting of SEQ ID NOs: 54 to 58, or includes an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 54 to 58. In some embodiments, the first VL includes an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 56. In some embodiments, the first VH includes an amino acid sequence selected from the group consisting of SEQ ID NOs. 48 to 53, or includes an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs. 48 to 53, and the first VL includes an amino acid sequence selected from the group consisting of SEQ ID NOs. 54 to 58, or includes an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs.In some embodiments, the first VH and the first VL each include the amino acid sequence shown below, or each includes an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs. 48 and 54, SEQ ID NOs. 49 and 55, SEQ ID NOs. 50 and 55, SEQ ID NOs. 50 and 56, SEQ ID NOs. 51 and 55, SEQ ID NOs. 51 and 56, SEQ ID NOs. 52 and 56, SEQ ID NOs. 53 and 57, or SEQ ID NOs. 50 and 58. In some embodiments, the first VH and the first VL each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs. 49 and 55, SEQ ID NOs. 50 and 55, SEQ ID NOs. 50 and 56, SEQ ID NOs. 51 and 55, or SEQ ID NOs. 51 and 56. In some embodiments, the first VH and the first VL each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs. 50 and 56. In some embodiments, the first VH and the first VL each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs. 51 and 56.In some embodiments, at least one of the first antigen-binding domain and the second antigen-binding domain independently comprises Fab, F(ab)2, Fv, scFv, sc(Fv)2, or a diabody. In some embodiments, the first antigen-binding domain comprises scFv and the second antigen-binding domain comprises Fab. In some embodiments, the first antigen-binding domain comprises scFv and the second antigen-binding domain comprises Fab, with the first VH and first VL comprising the amino acid sequences shown below, respectively: SEQ ID NOs: 50 and 56. In some embodiments, the first antigen-binding domain comprises Fab and the second antigen-binding domain comprises scFv. In some embodiments, the first antigen-binding domain comprises scFv and the second antigen-binding domain comprises scFv. In some embodiments, the first antigen-binding domain comprises Fab and the second antigen-binding domain comprises the extracellular domain of CD4. In some embodiments, the first antigen-binding domain comprises Fab, the second antigen-binding domain comprises the extracellular domain of CD4, and the first VH and first VL comprise the amino acid sequences shown below, respectively: SEQ ID NOs: 51 and 56. In some embodiments, the first antigen-binding domain comprises scFv, and the second antigen-binding domain comprises the extracellular domain of CD4. In some embodiments, the first antigen-binding domain is scFv, which comprises cysteine ​​(C) at position 44 of the scFv variable heavy domain and cysteine ​​(C) at position 100 of the scFv variable light domain. In some embodiments, the first antigen-binding domain is an scFv comprising VH and VL, the scFv comprising an amino acid sequence selected from SEQ ID NOs. 59 to 66, or comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence selected from SEQ ID NOs. 59 to 66.In some embodiments, the first antigen-binding domain is an scFv comprising VH and VL, wherein the scFv comprises an amino acid sequence selected from SEQ ID NOs. 59-63, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence selected from SEQ ID NOs.

[0015] Regarding further embodiments of a second antigen-binding domain of a multispecific (e.g., bispecific) antigen-binding molecule that targets or binds to an HIV antigen, in some embodiments, the second antigen-binding domain binds to an HIV envelope protein selected from the group consisting of gp120 and gp41. In some embodiments, the second antigen-binding domain binds to a broadly neutralizing antibody (bNAb) that binds to the HIV antigen. The second antigen-binding domain competes with or includes the VH and VL variable domains of ). In some embodiments, the second antigen-binding domain binds to an epitope or region of gp120 selected from the group consisting of a third variable loop (V3) containing N332 oligomannose glycan (e.g., a high-mannose patch), a second variable loop (V2) (e.g., an Env trimer apex), a CD4 binding site (CD4bs), a gp120 / gp41 interface, or a silent surface of gp120. In some embodiments, the second antigen-binding domain binds to an epitope or region of gp120 within a third variable loop (V3) containing N332 oligomannose glycan (e.g., a high-mannose patch), and to GS-9722 (elipovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-125, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, Competing with, or containing, the VH and VL regions derived from antibodies selected from the group consisting of PGT-136, PGT-137, PGT-138, PGT-139, 10-1074, 10-1074-J, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG42, 354BG33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03. In some embodiments, the second antigen-binding domain binds to an epitope or region of gp120 within a second variable loop (V2) (e.g., the Env trimer vertex) and competes with or includes VH and VL regions derived from an antibody selected from the group consisting of PG9, PG16, PGC14, PGG14, PGT-142, PGT-143, PGT-144, PGT-145, CH01, CH59, PGDM1400, CAP256, CAP256-VRC26.08, CAP256-VRC26.09, CAP256-VRC26.25, PCT64-24E, and VRC38.01.In some embodiments, the second antigen-binding domain binds to the gp120 epitope or region within the CD4 binding site (CD4bs), and is associated with 3BNC117, GS-9723, GS-5423, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, and VRC06b01. The second antigen-binding domain competes with or includes the VH and VL regions of antibodies selected from the group consisting of VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25. In some embodiments, the second antigen-binding domain binds to an epitope or region of gp120 within a CD4-binding site (CD4bs) and includes one or more extracellular (EC) domains of CD4. In some embodiments, one or more extracellular (EC) domains of CD4 include sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the sequences shown below or selected from the group consisting of: (i)KKVVYGKKGDTVELTCTASQKKNIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRVDSRRSLWDQGNFPLIIKNLKPEDSDTYICEVEDQKEEVQLVVVG (Sequence ID 746), (ii) KKVVYGKKGDTVELTCTASQKKNIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRVDSRRSLWDQGNFPLIIKNLKPEDSDTYICEVEDQKEEVQLVVVGGGGSGKKVVYGKKGDTVELTCTASQKKNIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRVDSRRSLWDQGNFPLIIKNLKPEDSDTYICEVEDQKEEVQLVVVG (Sequence ID 747), (iii)KKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQLLVFG (Sequence ID 748), or (iv)KKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQLLVFGGGGSGKKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQLLVFG (Sequence ID 749). In some embodiments, the C domain of CD4 contains a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99% identical to the sequence of sequence number 746. In some embodiments, the EC domain of CD4 contains a sequence that is at least 95% identical to the sequence of sequence number 746. In some embodiments, the EC domain of CD4 contains a sequence that is at least 99% identical to the sequence of sequence number 746. In some embodiments, the EC domain of CD4 contains the sequence of sequence number 746. In some embodiments, the second antigen-binding domain binds to an epitope or region of gp120 at the gp120 / gp41 interface and competes with or includes VH and VL regions derived from an antibody selected from the group consisting of PGT-151, CAP248-2B, 35O22, 8ANC195, ACS202, VRC34, and VRC34.01. In some embodiments, the second antigen-binding domain binds to an epitope or region of the gp120 silent surface and competes with or includes VH and VL regions derived from an antibody selected from VRC-PG05 and SF12. In some embodiments, the second antigen-binding domain binds to an epitope or region of gp41 in the membrane proximal region (MPER). In some embodiments, the second antigen-binding domain binds to an epitope or region of gp41 in the membrane proximal region (MPER) and competes with or includes VH and VL regions derived from an antibody selected from the group consisting of 10E8, 10E8v4, 10E8-5R-100cF, 4E10, DH511.11P, 2F5, 7b2, and LN01. In some embodiments, the second antigen-binding domain binds to an epitope or region of the gp41 fusion peptide and competes with or includes VH and VL regions derived from an antibody selected from the group consisting of VRC34 and ACS202. In some embodiments, the second antigen-binding domain includes a second VH, a second VH-CDR1, a second VH-CDR2, and a second VH-CDR3, and a second VL-CDR1, a second VL-CDR2,A second VL containing a second VH-CDR3, and each containing the following amino acid sequences (according to Kabat): SEQ ID NOs: 76, 77, 78, 79, 80, and 81; SEQ ID NOs: 76, 82, 78, 79, 80, and 81; SEQ ID NOs: 83, 84, 85, 86, 80, and 87; SEQ ID NOs: 83, 88, 85, 86, 80, and 87; SEQ ID NOs: 90, 91, 92, 93, 94, and 95; SEQ ID NOs: 90, 91, 96, 93, 94, and 95; SEQ ID NOs: 97, 98, 99, 100, 101, and 102; SEQ ID NOs: 103, 104, 105, 106, 94, and 107, SEQ ID NOs: 108, 109, 110, 111, 112, and 113, SEQ ID NOs: 114, 115, 116, 117, 118, and 119, SEQ ID NOs: 114, 120, 121, 122, 118, and 123, SEQ ID NOs: 124, 125, 126, 127, 128, and 113, SEQ ID NOs: 129, 115, 131, 127, 118, and 113, SEQ ID NOs: 132, 133, 134, 135, 136, and 137, SEQ ID NOs: 138, 139, 140, 141, 142, and 143, SEQ ID NOs: 144, 145, 146, 147, 148, and 143, SEQ ID NOs: 149, 150, 151, 152, 153, and 143, SEQ ID NOs: 154, 155, 156, 157, 158, and 159, SEQ ID NOs: 160, 161, 162, 163, 164, and 165, SEQ ID NOs: 166, 161, 167, 163, 164, and 165, SEQ ID NOs: 168, 169, 170, 171, 172, and 173, SEQ ID NOs: 168, 174, 170, 171, 172, and 173, SEQ ID NOs: 175, 176, 177, 171, 172, and 173, SEQ ID NOs: 178, 179, 180, 181, 182, and 183, SEQ ID NOs: 184, 185, 18 6, 187, 188, and 189, Sequence IDs 190, 191, 192, 193, 194, and 195, Sequence IDs 196, 197, 198, 199, 200, and 201, Sequence IDs 202, 203, 204, 205, 206, and 207, Sequence IDs 208, 209, 210, 211, 212, and 213, Sequence IDs 214, 215, 216, 217, 218, and 219, Sequence IDs 214, 220, 216, 221, 218, and 219, Sequence IDs 214, 220, 222, 221, 218, and 219, Sequence IDs 223, 224, 225, 226, 227,and 228, sequence numbers 229, 230, 231, 232, 233, and 234, sequence numbers 902, 903, 904, 905, 906, and 907, sequence numbers 908, 909, 910, 911, 912, and 913, sequence numbers 914, 915, 916, 917, 918, and 919, or sequence numbers 920, 921, 922, 923, 924, and 925. In some embodiments, the second antigen-binding domain comprises a second VH comprising a second VH-CDR1, a second VH-CDR2, and a second VH-CDR3, and a second VL comprising a second VL-CDR1, a second VL-CDR2, and a second VH-CDR3, respectively, with the following amino acid sequences (according to Chothia): SEQ ID NOs. 235, 236, 237, 238, 239, and 240, SEQ ID NOs. 241, 242, 243, 244, 239, and 245. Sequence numbers 246, 242, 247, 244, 239, and 245, Sequence numbers 248, 249, 250, 251, 239, and 252, Sequence numbers 248, 249, 253, 251, 239, and 252, Sequence numbers 254, 255, 256, 257, 258, and 259, Sequence numbers 260, 261, 262, 263, 239, and 264, Sequence numbers 265, 266, 267, 268, 269, and 270, Sequence numbers 271, 272, 273, 274, 275, and 270, Sequence numbers 271, 276, 277, 278, 275, and 279, Sequence numbers 280, 281, 282, 283, 284, and 270, Sequence numbers 285, 272, 286, 283, 275, and 270, Sequence numbers 287, 288, 289, 290, 291, and 292, Sequence numbers 293, 294, 295, 296, 297, and 298, Sequence numbers 299, 300, 301, 302, 303, and 298, Sequence numbers 304, 300, 305, 406, 307, and 298, Sequence numbers 308, 309, 310, 311, 312, and 313, Sequence numbers 314, 315, 316, 317, 318, and 165, Sequence numbers 320, 315, 321, 317, 318, and 165, Sequence numbers 322, 323, 324, 325, 326, and 327, Sequence numbers 322, 328, 324, 325, 326, and 327, Sequence numbers 329, 323, 330, 325, 326, and 327, Sequence numbers 331, 332, 333, 334, 335, and 336,Sequence numbers 337, 338, 339, 340, 341, and 342, Sequence numbers 343, 344, 345, 346, 341, and 347, Sequence numbers 348, 349, 350, 351, 352, and 353, Sequence numbers 354, 355, 356, 357, 358, and 359, Sequence numbers 360, 361, 362, 363, 364, and 365, Sequence numbers 366, 367, 368, 369, 370, and 371, Sequence numbers 366, 361, 368, 369, 370, and 371, Sequence number Includes numbers 372, 361, 373, 369, 370, and 371, sequence numbers 374, 375, 376, 377, 378, and 379, sequence numbers 380, 381, 382, ​​383, 384, and 385, sequence numbers 926, 927, 928, 929, 930, and 931, sequence numbers 932, 933, 934, 935, 936, and 937, sequence numbers 938, 939, 940, 941, 942, and 943, or sequence numbers 944, 945, 946, 947, 948, and 949. In some embodiments, the second antigen-binding domain comprises a second VH domain including a second VH-CDR1, a second VH-CDR2, and a second VH-CDR3, and a second VL domain including a second VL-CDR1, a second VL-CDR2, and a second VH-CDR3, each with the following amino acid sequences (according to IMGT): SEQ ID NOs: 386, 387, 388, 389, 239, and 81; SEQ ID NOs: 390, 391, 392, 393, 239, and 87; SEQ ID NOs: 390, 391, 394, 393, 239, and 87; SEQ ID NOs: 395, 396, 397, 393, 239, and 87; SEQ ID NOs: 398, 399, 400, 401, and 239 , and 95, SEQ ID NOs: 398, 399, 402, 401, 239, and 95, SEQ ID NOs: 403, 404, 405, 406, 258, and 102, SEQ ID NOs: 407, 408, 409, 410, 239, and 107, SEQ ID NOs: 411, 412, 413, 414, 269, and 113, SEQ ID NOs: 415, 416, 417, 41 8, 275, and 119, Sequence IDs 415, 419, 420, 421, 275, and 123, Sequence IDs 422, 423, 424, 425, 275, and 113, Sequence IDs 426, 416, 427, 425, 275, and 113, Sequence IDs 428, 429, 430, 431, 291, and 137, Sequence IDs 432, 433,434, 435, 297, and 143, SEQ ID NOs: 436, 437, 438, 439, 303, and 143, SEQ ID NOs: 440, 437, 441, 442, 307, and 143, SEQ ID NOs: 443, 444, 445, 446, 312, and 159, SEQ ID NOs: 447, 448, 449, 450, 318, and 165, SEQ ID NOs: 451, 448, 452, 450, 318, and 165, SEQ ID NOs: 453, 45 4, 455, 456, 326, and 173, Sequence IDs 453, 457, 455, 456, 326, and 173, Sequence IDs 458, 459, 460, 456, 326, and 173, Sequence IDs 461, 462, 463, 464, 335, and 183, Sequence IDs 465, 466, 467, 468, 341, and 189, Sequence IDs 469, 470, 471, 472, 341, and 195, Sequence ID 473, 474, 475, 476, 352, and 201, Sequence IDs 477, 478, 479, 480, 358, and 207, Sequence IDs 481, 482, 483, 484, 364, and 213, Sequence IDs 485, 486, 487, 488, 370, and 219, Sequence IDs 485, 482, 487, 488, 370, and 219, Sequence IDs 489, 482, 490, 488, 370, and 219, Sequence ID 49 Includes sequences 1, 492, 493, 494, 378, and 228, sequences 495, 496, 497, 498, 384, and 234, sequences 950, 951, 952, 953, 930, and 907, sequences 954, 955, 956, 957, 936, and 913, sequences 958, 959, 960, 961, 942, and 919, or sequences 962, 963, 964, 965, 948, and 925. In some embodiments, the second antigen-binding domain comprises a second VH comprising a second VH-CDR1, a second VH-CDR2, and a second VH-CDR3, and a second VL comprising a second VL-CDR1, a second VL-CDR2, and a second VH-CDR3, each with the following amino acid sequences (according to Honegger): SEQ ID NOs: 499, 500, 501, 238, 502, and 240; SEQ ID NOs: 499, 503, 501, 238, 502, and 240; SEQ ID NOs: 505, 506, 507, 244, 502, and 245; SEQ ID NOs: 508, 509, 510, 244, 502, and 245; SEQ ID NOs: 511, 512, 513,251, 514, and 252, Sequence IDs 511, 512, 515, 251, 514, and 252, Sequence IDs 516, 517, 518, 257, 519, and 259, Sequence IDs 520, 521, 522, 264, 523, and 264, Sequence IDs 524, 525, 526, 268, 527, and 270, Sequence ID 528, , 529, 530, 274, 531, and 270, Sequence IDs 528, 532, 533, 278, 531, and 279, Sequence IDs 534, 535, 536, 283, 537, and 270, Sequence IDs 1090, 529, 538, 283, 531, and 270, Sequence IDs 539, 540, 541, 290, 542, and 292, Sequence IDs 543, 544, 545, 546, 547, and 298, Sequence IDs 548, 549, 550, 1091, 551, and 298, Sequence IDs 552, 553, 554, 555, 556, and 298; Sequence IDs 557, 558, 559, 311, 560, and 313; Sequence IDs 561, 562, 563, 564, 565, and 165; Sequence IDs 566, 562, 1092, 564, 567, and 165; Sequence IDs 568, 569, 570, 571, 572, and 327; Sequence IDs 568, 573, 570, 571, 572, and 327; Sequence IDs 574, 575, 576, 571, 572, and 327; Sequence IDs 577, 578, 579, and 580 , 581, and 336, SEQ ID NOs: 582, 583, 584, 340, 585, and 342, SEQ ID NOs: 586, 587, 588, 346, 589, and 347, SEQ ID NOs: 590, 591, 592, 351, 593, and 353, SEQ ID NOs: 594, 595, 596, 597, 598, and 359, SEQ ID NOs: 599, 600, 601, 602, 603, and 365, SEQ ID NOs: 604, 605, 606, 607, 608, and 371, SEQ ID NOs: 604, 609, 606, 607, 608, and 3 Includes 71, SEQ ID NOs: 610, 609, 611, 607, 608, and 371, SEQ ID NOs: 612, 613, 614, 615, 616, and 379, SEQ ID NOs: 617, 618, 619, 620, 621, and 385, SEQ ID NOs: 966, 967, 968, 969, 970, and 931, SEQ ID NOs: 971, 972, 973, 974, 975, and 937, SEQ ID NOs: 976, 977, 978, 941, 979, and 943, or SEQ ID NOs: 980, 981, 982, 983, 984, and 949. In some embodiments, the second VH and the second VL each contain the amino acid sequence shown below, or each contains the amino acid sequence shown below and at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%,Contains amino acid sequences that are at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical: SEQ ID NOs. 622 and 623, SEQ ID NOs. 624 and 625, SEQ ID NOs. 624 and 626, SEQ ID NOs. 627 and 628, SEQ ID NOs. 629 and 630, SEQ ID NOs. 631 and 632, SEQ ID NOs. 633 and 634, SEQ ID NOs. 635 and 636, SEQ ID NOs. 637 and 638, SEQ ID NOs. 639 and 640, SEQ ID NOs. 641 and 642, SEQ ID NOs. 643 and 644, SEQ ID NOs. 645 and 646, SEQ ID NOs. 647 and 648, SEQ ID NOs. 649 and 650, SEQ ID NOs. 651 and 652, SEQ ID NOs. 653 and 654, SEQ ID NOs. 655 and 656, SEQ ID NOs. 657 and 658, SEQ ID NOs. 659 and 660, SEQ ID NOs. 661 and 662, SEQ ID NOs. 663 and 664, SEQ ID NOs. 665 and 666, SEQ ID NOs. 667 and 668, SEQ ID NOs. 669 and 670, SEQ ID NOs. 671 and 672, SEQ ID NOs. 673 and 670, SEQ ID NOs. 674 and 675, SEQ ID NOs. 676 and 677, SEQ ID NOs. 678 and 679, SEQ ID NOs. 680 and 681, SEQ ID NOs. 682 and 683, SEQ ID NOs. 684 and 685, SEQ ID NOs. 686 and 687, SEQ ID NOs. 688 and 689, SEQ ID NOs. 690 and 691, SEQ ID NOs. 692 and 693, SEQ ID NOs. 694 and 695, SEQ ID NOs. 985 and 986, SEQ ID NOs. 987 and 988, SEQ ID NOs. 989 and 990, or SEQ ID NOs. 991 and 992. In some embodiments, the second VH and the second VL are identical to the amino acid sequence shown below by at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, respectively, and contain the following amino acids at the positions shown below (position numbering follows Kabat): (i) Ser-Ser-Val (SSV) or Thr-Gly-Val (TGV) at positions 82a-82c, Gln (Q) at position 39, Asn (N) at position 60, His (H) at position 68, one of Lys (K), His (H), or Thr (T) at position 105, one or more of Leu (L) at position 2, Ala (A) at position 32, and Ala (A) at position 95, as shown in SEQ ID NOs. 622, 624.Alternatively, sequence numbers 623, 625, 626, or 628, which include one or more of the following: Gly (G) at position 67, Tyr (Y), Phe (F), or Thr (T) at position 67a, Arg (R) at position 67b, Pro (P) at position 67c, and Lys (K) at position 103, or (ii) His (H) at position 3, Ser (S) or Val (V) at position 5, Glu (E) at position 10, Lys (K) at position 12, Lys (K) at position 23, Asn (N) at position 28, and Arg at position 30 (R), 32nd Tyr(Y), 68th Thr(T), 69th Met(M), 72nd Gln(Q) or His(H), 74ath Tyr(Y), Phe(F), 76th Phe(F) or Ser(S), 77th Ser(S), 78th Ala(A), 82ath Ser(S), 82bth Arg(R), 82cth Val(V), 89th Ile(I) or Thr(T), 98th Phe(F), 99th Tyr(Y) or Gly(G), 105 Sequence numbers 663, 665, or 667, which include one or more of the following: Gln(Q) at position 108, Met(M) at position 108, Phe-Asp-Phe-Asp(FDFD) (sequence number 1040) at positions 74a, 74b, 74c, and 74d, and Trp-Asp-Phe-Asp(WDFD) (sequence number 1042) at positions 74a, 74b, 74c, and 74d, as well as Arg(R) at position 14, Arg(R) at position 18, Ala(A) at position 19, Lys(L) at position 39, and Pro( P), the amino acid sequence containing one or more of the following: Thr (T) at position 56, Ala (A) at position 60, Ser (S) at position 65, Thr (T) or His (H) at position 72, Lys (K) at position 74, Ser (S) at position 76, Ser (S) at position 77, Val (V) at position 83, Ile (I) or Phe (F) at position 98, Thr (T) or Gly (G) at position 99, Asn (N) at position 103, and Ile (I) at position 106, including sequence numbers 664, 666, or 668. In some embodiments, the second VH and the second VL each contain the amino acid sequence shown below, and at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%,Alternatively, they are at least 99% identical and contain one or more of the following amino acids at the positions shown below (position numbering follows Kabat): (i) Thr-Gly-Val (TGV) at positions 82a-82c, Asn (N) at position 60, His (H) at position 68, Lys (K), His (H), and Thr (T) at position 105, as in sequence numbers 622, 624, or 627, and Gl at position 67. The amino acid sequences include (ii) one or more of the following: y(G), Tyr(Y) at position 67a, Phe(F), or Thr(T), Arg(R) at position 67b, or Pro(P) at position 67c, as in sequence numbers 623, 625, 626, or 628, or (ii) sequence numbers 663, 665, or 667, which include Phe(F) at position 74a, and sequence numbers 664, 666, or 668, which include Ala(A) at position 19.

[0016] With respect to the first and second Fc regions or domains of the multispecific antigen-binding molecule, in some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises a heterodimer human IgG1 or IgG4 including a first Fc region and a second Fc region. In some embodiments, the first and second Fc regions do not originate from IgG1m17. In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises a heterodimer human IgG1 or IgG4 including a first Fc region and a second Fc region, and one or both of the first and second Fc regions contain one or more of the following amino acids at the indicated position (EU numbering): alanine at position 234, alanine at position 235, and serine at position 331. In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises a heterodimer human IgG1 having a first Fc region and a second Fc region, both of which contain one or more of the following amino acids at the indicated positions (EU numbering): alanine at position 234, alanine at position 235, and serine at position 331. In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises a heterodimer human IgG1 or IgG4 having a first Fc region and a second Fc region, one or both of the first and second Fc regions containing the following amino acids at the indicated positions (EU numbering): tyrosine at position 252, threonine at position 254, and glutamic acid (YTE) at position 256, or leucine at position 428 and phosphorus (LS) at position 434. In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises a heterodimer human IgG1 having a first Fc region and a second Fc region, one of the first and second Fc regions containing the following amino acids at the indicated positions (EU numbering): tyrosine at position 252, threonine at position 254, and serine at position 256 (YTE). In some embodiments, multispecific (e.g.,The bispecific antigen-binding molecule contains a heterodimer human IgG1 comprising a first Fc region and a second Fc region, the second Fc region containing the following amino acids at the indicated position (EU numbering): tyrosine at position 252, threonine at position 254, and glutamic acid (YTE) at position 256. In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises a heterodimer human IgG1 or IgG4 having a first Fc region and a second Fc region, with the following amino acids at the indicated position (EU numbering): the first Fc region having tryptophan at position 366 (T366W), and the second Fc region having serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V); the first Fc region having serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V), and the second Fc region having tryptophan at position 366 Contains liptophan (T366W); the first Fc region contains cysteine ​​at position 354 (S354C) and tryptophan at position 366 (T366W), and the second Fc region contains cysteine ​​at position 349 (Y349C), serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V); the first Fc region contains cysteine ​​at position 349 (Y349C), serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V), and the second Fc region contains cysteine ​​at position 354 (S354C) and tryptophan at position 366 (T366W). In some embodiments, a multispecific (e.g., bispecific) antigen-binding molecule comprises a heterodimer human IgG1 comprising a first Fc region and a second Fc region, with the following amino acids at the indicated positions (EU numbering): the first Fc region comprises tryptophan at position 366 (T366W), and the second Fc region comprises serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V); or the first Fc region comprises serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V), and the second Fc region comprises tryptophan at position 366 (T366W). In some embodiments, multispecific (e.g.,The bispecific antigen-binding molecule comprises a heterodimer human IgG1 containing a first Fc region and a second Fc region, with the following amino acids at the indicated positions (EU numbering): the first Fc region contains serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V); and the second Fc region contains tryptophan at position 366 (T366W). In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises a heterodimer human IgG1 or IgG4 containing a first hinge region and a second hinge region, with one or both of the first and second hinge regions containing serine at position 220 (C220S) (EU numbering). In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises a heterodimer human IgG1 or IgG4 having a first Fc region and a second Fc region, wherein one of the first or second Fc region contains the following amino acids at the indicated position (EU numbering): arginine (H435R) at position 435, or arginine (H435R) at position 435 and phenylalanine (Y436F) at position 436. In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises a heterodimer human IgG1 having a first Fc region and a second Fc region, wherein the first Fc region contains arginine (H435R) at position 435. In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises a heterodimer human IgG1 comprising a first Fc region and a second Fc region, with the following amino acids at the indicated positions (EU numbering): the first Fc region comprises alanine (L234) at position 234, alanine (L235A) at position 235, serine (P331S) at position 331, and tryptophan (T366W) at position 366; and the second Fc region comprises alanine (L234) at position 234, alanine (L235A) at position 235, serine (P331S) at position 331, and serine (T366S) at position 366.The first Fc region contains alanine at position 368 (L368A), valine at position 407 (Y407V), and arginine at position 435 (H435R); the second Fc region contains alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), and tryptophan at position 366 (T366W); and the second Fc region contains alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V The first Fc region includes arginine at position 435 (H435R) and phenylalanine at position 436 (Y436F); the first Fc region includes alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V); the second Fc region includes alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), and tryptophan at position 366 (T366W); the first The Fc region includes alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), tryptophan at position 366 (T366W), leucine at position 428 (M428L), and serine at position 434 (N434S), and the second Fc region includes alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), serine at position 366 (T366S), alanine at position 368 (L368A), valine at position 407 (Y407V), and arginine at position 435 (H435R); also The first Fc region contains alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), tryptophan at position 366 (T366W), tyrosine at position 252 (M252Y), threonine at position 254 (S254T), and glutamic acid at position 256 (T256E), and the second Fc region contains alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V),and arginine at position 435 (H435R). In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises a heterodimer human IgG1 comprising a first Fc region and a second Fc region, and containing the following amino acids at the indicated positions (EU numbering): the first Fc region contains alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), serine at position 366 (T366S), and alanine at position 368 ( The second Fc region contains L368A, valine at position 407 (Y407V), and arginine at position 435 (H435R), and the second Fc region contains alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), tryptophan at position 366 (T366W), tyrosine at position 252 (M252Y), threonine at position 254 (S254T), and glutamic acid at position 256 (T256E). In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecules each include a heterodimer human IgG1 comprising a first Fc region and a second Fc region each comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs. 696 and 697, SEQ ID NOs. 697 and 697 96, SEQ ID NOs. 696 and 698, SEQ ID NOs. 698 and 696, SEQ ID NOs. 699 and 700, SEQ ID NOs. 700 and 699, SEQ ID NOs. 701 and 698, SEQ ID NOs. 698 and 701, SEQ ID NOs. 702 and 703, SEQ ID NOs. 703 and 702, SEQ ID NOs. 704 and 698, SEQ ID NOs. 698 and 704, SEQ ID NOs. 705 and 703, SEQ ID NOs. 703 and 705, SEQ ID NOs. 706 and 704, SEQ ID NOs. 704 and 706, SEQ ID NOs. 707 and 703, SEQ ID NOs. 703 and 707, SEQ ID NOs. 708 and 704, SEQ ID NOs. 704 and 708, SEQ ID NOs. 709 and 710, or SEQ ID NOs. 710 and 709. In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecules each have the amino acid sequence shown below, and at least 80%, at least 85%, at least 90%,Heterodimer human IgG1 comprising a first Fc region and a second Fc region having amino acid sequences that are at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical: SEQ ID NOs. 703 and 705. In some embodiments, multiple, The specific (e.g., bispecific) antigen-binding molecules include heterodimer human IgG1 comprising a first Fc region and a second Fc region, each containing an amino acid sequence that is at least 95% identical to the amino acid sequence shown below: SEQ ID NOs: 703 and 705. In some embodiments, the multiple specific (e.g., bispecific) antigen-binding molecules include heterodimer human IgG1 comprising a first Fc region and a second Fc region, each containing an amino acid sequence that is at least 99% identical to the amino acid sequence shown below: SEQ ID NOs: 703 and 705. In some embodiments, the multiple specific (e.g., bispecific) antigen-binding molecules include heterodimer human IgG1 comprising a first Fc region and a second Fc region, each containing an amino acid sequence that is at least 99% identical to the amino acid sequence shown below: SEQ ID NOs: 703 and 705.

[0017] Regarding further embodiments of multispecific (e.g., bispecific) antigen-binding molecules, in some embodiments, the first antigen-binding domain is scFv that binds to CD3, the second antigen-binding domain is Fab that binds to HIV gp120, the first antigen-binding domain comprises a first heavy chain (HC), the second antigen-binding domain comprises a second HC and a light chain (LC), and the first HC, second HC, and LC each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: sequence number Sequence numbers 800, 801, and 802; Sequence numbers 800, 803, and 802; Sequence numbers 804, 803, and 802; Sequence numbers 804, 805, and 802; Sequence numbers 806, 801, and 802; Sequence numbers 806, 803, and 802; Sequence numbers 807, 803, and 802; Sequence numbers 807, 805, and 802; Sequence numbers 808, 809, and 802; Sequence numbers 808, 810, and 802; Sequence numbers 811, 801, and 802; Sequence numbers 812, 809 , and 802, Sequence IDs 812, 810, and 802, Sequence IDs 813, 805, and 802, Sequence IDs 812, 814, and 802, Sequence IDs 815, 801, and 802, Sequence IDs 816, 805, and 802, Sequence IDs 817, 801, and 802, Sequence IDs 818, 805, and 802, Sequence IDs 819, 810, and 802, Sequence IDs 820, 810, and 802, Sequence IDs 821, 822, and 823, Sequence IDs 824, 825, and 823, Sequence numbers 826, 825, and 823, Sequence numbers 826, 827, and 823, Sequence numbers 828, 829, and 823, Sequence numbers 830, 822, and 823, Sequence numbers 830, 825, and 823, Sequence numbers 831, 825, and 823, Sequence numbers 831, 827, and 823, Sequence numbers 832, 833, and 823, Sequence numbers 832, 829, and 823, Sequence numbers 834, 827, and 823, Sequence numbers 835, 829, and 823, Sequence number 836,829, and 823, Sequence IDs 837, 833, and 823, Sequence IDs 837, 838, and 823, Sequence IDs 839, 840, and 823, Sequence IDs 841, 829, and 823, Sequence IDs 842, 829, and 823, Sequence IDs 843, 829, and 823, Sequence IDs 844, 829, and 823, Sequence IDs 845, 829, and 823, Sequence IDs 846, 829, and 823, Sequence IDs 846, 833, and 823, Sequence IDs 846, 838, and 823, Sequence IDs 847, 827, and 823, Sequence IDs 848, 829, and 823, Sequence ID 84 9, 829, and 823, Sequence IDs 850, 829, and 823, Sequence IDs 851, 829, and 823, Sequence IDs 852, 829, and 823, Sequence IDs 853, 829, and 823, Sequence IDs 854, 829, and 823, Sequence IDs 855, 829, and 823, Sequence IDs 856, 829, and 823, Sequence IDs 857, 829, and 823, Sequence IDs 858, 829, and 823, Sequence IDs 859, 829, and 823, Sequence IDs 860, 829, and 823, Sequence IDs 861, 862, and 863, Sequence IDs 861, 864, and 863, Sequence ID 865, 864, and 863, sequence numbers 865, 866, and 863, sequence numbers 867, 868, and 863, sequence numbers 869, 862, and 863, sequence numbers 869, 864, and 863, sequence numbers 870, 864, and 863, sequence numbers 870, 866, and 863, sequence numbers 871, 872, and 863, sequence numbers 871, 868, and 863, sequence numbers 873, 862, and 863, sequence numbers 874, 866, and 863, sequence numbers 875, 872, and 863, sequence numbers 875, 868, and 863, sequence numbers 875, 876, and 863, sequence numbers Numbers 877, 862, and 863, Sequence numbers 878, 866, and 863, Sequence numbers 879, 862, and 863, Sequence numbers 880, 866, and 863, Sequence numbers 881, 882, and 883, Sequence numbers 881, 884, and 883, Sequence numbers 885, 884, and 883, Sequence numbers 885, 886, and 883, Sequence numbers 887, 888, and 883, Sequence numbers 889, 882, and 883, Sequence numbers 889, 884, and 883, Sequence numbers 890, 884, and 883, Sequence numbers 890, 886, and 883, Sequence numbers 891, 892, and 883,SEQ ID NOs: 891, 888, and 883, SEQ ID NOs: 893, 882, and 883, SEQ ID NOs: 894, 886, and 883, SEQ ID NOs: 895, 892, and 883, SEQ ID NOs: 895, 888, and 883, SEQ ID NOs: 895, 896, and 883, SEQ ID NOs: 897, 882, and 883, SEQ ID NOs: 898, 886, and 883, SEQ ID NOs: 899, 882, and 883, or SEQ ID NOs: 900, 886, and 883. In some embodiments, the first antigen-binding domain is an scFv that binds to CD3, and the second antigen-binding domain is HIV Fabs that bind to gp120, wherein the first antigen-binding domain comprises a first heavy chain (HC), and the second antigen-binding domain comprises a second HC and a light chain (LC), and the first HC, second HC, and LC each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs: 800, 801, and 802; SEQ ID NOs: 800, 803, and 802; SEQ ID NOs: 804, 803, and 802; SEQ ID NOs: 804, 805, and 802; SEQ ID NOs: 806, 801, and 802; SEQ ID NOs: 806, 803, and 802; SEQ ID NOs: 807, 803 , and 802, sequence numbers 807, 805, and 802, sequence numbers 808, 809, and 802, sequence numbers 808, 810, and 802, sequence numbers 821, 822, and 823, sequence numbers 824, 825, and 823, sequence numbers 826, 825, and 823, sequence numbers 826, 827, and 823, sequence numbers 828, 829, and 823, sequence numbers 830, 822, and 823, sequence numbers 830, 825, and 823, sequence Numbers 831, 825, and 823, Sequence numbers 831, 827, and 823, Sequence numbers 832, 833, and 823, Sequence numbers 832, 829, and 823, Sequence numbers 861, 862, and 863, Sequence numbers 861, 864, and 863, Sequence numbers 865, 864, and 863, Sequence numbers 865, 866, and 863, Sequence numbers 867, 868, and 863, Sequence numbers 869, 862, and 863, Sequence numbers 869, 864,and 863, SEQ ID NOs: 870, 864, and 863, SEQ ID NOs: 870, 866, and 863, SEQ ID NOs: 871, 872, and 863, SEQ ID NOs: 871, 868, and 863, SEQ ID NOs: 881, 882, and 883, SEQ ID NOs: 881, 884, and 883, SEQ ID NOs: 885, 884, and 883, SEQ ID NOs: 885, 886, and 883, SEQ ID NOs: 887, 888, and 883, SEQ ID NOs: 889, 882, and 883, SEQ ID NOs: 889, 884, and 883, SEQ ID NOs: 890, 884, and 883, SEQ ID NOs: 890, 886, and 883, SEQ ID NOs: 891, 892, and 883, or SEQ ID NOs: 891, 888, and 883. In some embodiments, the first antigen-binding domain is an scFv that binds to CD3, and the second antigen-binding domain is HIV A Fab that binds to gp120, wherein the first antigen-binding domain comprises a first heavy chain (HC), and the second antigen-binding domain comprises a second HC and a light chain (LC), and the first HC, second HC, and LC each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs: 800, 801, and 802, SEQ ID NOs: 800, 803, and 802, SEQ ID NOs: 80 4, 803, and 802, Sequence IDs 804, 805, and 802, Sequence IDs 821, 822, and 823, Sequence IDs 824, 825, and 823, Sequence IDs 826, 825, and 823, Sequence IDs 826, 827, and 823, Sequence IDs 828, 829, and 823, Sequence IDs 861, 862, and 863, Sequence IDs 861, 864, and 863, Sequence IDs 865, 864, and 863, Sequence IDs 865, 866, and 863, Sequence IDs 867, 868, and 863, Sequence IDs 881, 882, and 883, Sequence IDs 881, 884, and 883, Sequence IDs 885, 884, and 883, Sequence IDs 885, 886, and 883, or Sequence IDs 887, 888, and 883. In some embodiments, the first antigen-binding domain is an scFv that binds to CD3, and the second antigen-binding domain isFab that binds to HIV gp120, wherein the first antigen-binding domain comprises a first heavy chain (HC), and the second antigen-binding domain comprises a second HC and a light chain (LC), and the first HC, second HC, and LC each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below. Includes: Sequence IDs 800, 801, and 802; Sequence IDs 800, 803, and 802; Sequence IDs 804, 803, and 802; Sequence IDs 804, 805, and 802; Sequence IDs 821, 822, and 823; Sequence IDs 824, 825, and 823; Sequence IDs 826, 825, and 823; Sequence IDs 826, 827, and 823; Sequence IDs 828, 829, and 823; Sequence IDs 861, 862, and 863; Sequence IDs 861, 864, and 863; Sequence IDs 865, 864, and 863; Sequence IDs 865, 866, and 863; or Sequence IDs 867, 868, and 863.

[0018] Regarding further embodiments of multispecific (e.g., bispecific) antigen-binding molecules, in some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule comprises: (a) a first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), wherein the first antigen-binding domain binds to CD3; and (b) a second antigen-binding domain binding to HIV gp120 comprising one or more extracellular (EC) domains of CD4, wherein one or more EC domains of CD4 are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the sequences shown below or selected from the group consisting of: (i)KKVVYGKKGDTVELTCTASQKKNIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRVDSRRSLWDQGNFPLIIKNLKPEDSDTYICEVEDQKEEVQLVVVG (Sequence ID 746), (ii) KKVVYGKKGDTVELTCTASQKKNIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRVDSRRSLWDQGNFPLIIKNLKPEDSDTYICEVEDQKEEVQLVVVGGGGSGKKVVYGKKGDTVELTCTASQKKNIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRVDSRRSLWDQGNFPLIIKNLKPEDSDTYICEVEDQKEEVQLVVVG (Sequence ID 747), (iii)KKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQLLVFG (Sequence ID 748), or (iv)KKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQLLVFGGGGSGKKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQLLVFG (Sequence ID 749). In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 11, 8, 4, 9, and 10, or SEQ ID NOs: 1, 12, 8, 4, 9, and 10, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746 to 749, for example, SEQ ID NO: 746, or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 12, 8, 4, 9, and 10, and the second antigen-binding domain comprises one EC domain of CD4 containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the CD4 EC domain of SEQ ID NO: 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 12, 8, 4, 9, and 10, respectively, and the second antigen-binding domain comprises one EC domain of CD4, each containing an amino acid sequence that is at least 95% identical to the CD4 EC domain of SEQ ID NO: 746.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 12, 8, 4, 9, and 10, respectively, and the second antigen-binding domain comprises one EC domain of CD4, each containing an amino acid sequence that is at least 99% identical to the CD4 EC domain of SEQ ID NO: 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 12, 8, 4, 9, and 10, respectively, and the second antigen-binding domain comprises one EC domain of CD4 containing the amino acid sequence of SEQ ID NO: 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Chothia): SEQ ID NOs: 17, 18, 23, 20, 24, and 25, respectively, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746 to 749, for example, from SEQ ID NO: 746, or one or more CD4 EC domains comprising amino acid sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Chothia): SEQ ID NOs: 17, 18, 23, 20, 24, and 25, and the second antigen-binding domain comprises one EC domain of CD4, each containing an amino acid sequence that is at least 95% (e.g., at least 96%, at least 97%, at least 98%, or at least 99%) identical to the CD4 EC domain of SEQ ID NO: 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Chothia): SEQ ID NOs: 17, 18, 23, 20, 24, and 25, respectively, and the second antigen-binding domain comprises one EC domain of CD4 containing the amino acid sequence of SEQ ID NO: 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10, respectively, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746 to 749, for example, from SEQ ID NO. 746, or one or more CD4 EC domains comprising amino acid sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10, respectively, and the second antigen-binding domain comprises one EC domain of CD4, each containing an amino acid sequence that is at least 95% (e.g., at least 96%, at least 97%, at least 98%, or at least 99%) identical to the CD4 EC domain of SEQ ID NO. 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10, respectively, and the second antigen-binding domain comprises one EC domain of CD4 containing the amino acid sequence of SEQ ID NO. 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 42, 40, 37, 41, and 25, or SEQ ID NOs: 34, 43, 40, 37, 41, and 25, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746 to 749, for example, SEQ ID NO: 746, or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 43, 40, 37, 41, and 25, respectively, and the second antigen-binding domain comprises the CD4 EC domain of SEQ ID NO: 746, or one EC domain of CD4 comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 43, 40, 37, 41, and 25, respectively, and the second antigen-binding domain comprises one EC domain of CD4, comprising an amino acid sequence that is at least 95% (e.g., at least 96%, at least 97%, at least 98%, or at least 99%) identical to the CD4 EC domain of SEQ ID NO: 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 43, 40, 37, 41, and 25, respectively, and the second antigen-binding domain comprises one EC domain of CD4 containing the amino acid sequence of SEQ ID NO: 746.In some embodiments, the first antigen-binding domain comprises a first VH and a first VL, each containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequences: SEQ ID NOs: 49 and 55, SEQ ID NOs: 50 and 55, SEQ ID NOs: 50 and 56, SEQ ID NOs: 51 and 55, or SEQ ID NOs: 51 and 56, and the second antigen-binding domain comprises a CD4 selected from the group consisting of SEQ ID NOs: 746 to 749, for example, SEQ ID NO: 746. The CD4 contains an EC domain, or one or more EC domains of CD4 containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain includes a first VH and a first VL, each containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequences shown below: SEQ ID NOs. 50 and 56, and the second antigen-binding domain includes one EC domain of CD4, each containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the CD4 EC domain of SEQ ID NOs. 746. In some embodiments, the first antigen-binding domain comprises, respectively, the amino acid sequences shown below: SEQ ID NOs: 51 and 56, in amounts of at least 80%, at least 85%, at least 90%, at least 91%, and at least 92%. The first VH and first VL include an amino acid sequence that is at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, and the second antigen-binding domain includes one EC domain of CD4 that includes an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the CD4 EC domain of SEQ ID NO: 746.In some embodiments, the first antigen-binding domain is a Fab that binds to CD3, and the second antigen-binding domain is an scFv or CD4 EC domain that binds to HIV gp120, and the first antigen-binding domain includes a first HC and LC, and the second antigen-binding domain includes a second HC, and the second HC, the first HC, and LC each include the amino acid sequence shown below, or each includes the amino acid sequence shown below, and at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, and Includes amino acid sequences that are 97%, at least 98%, or at least 99% identical: SEQ ID NOs. 751, 752, and 753; SEQ ID NOs. 754, 752, and 753; SEQ ID NOs. 755, 756, and 753; SEQ ID NOs. 755, 757, and 753; SEQ ID NOs. 758, 757, and 753; SEQ ID NOs. 759, 756, and 753; SEQ ID NOs. 754, 760, and 761; SEQ ID NOs. 762, 760, and 761; SEQ ID NOs. 751, 763, and 753; SEQ ID NOs. 764, 752, and 753; SEQ ID NOs. 7560, and 761; SEQ ID NOs. 762, 760, and 761; SEQ ID NOs. 751, 763, and 753; SEQ ID NOs. 764, 752, and 753; SEQ ID NOs. 754, 752, and 753; SEQ ID NOs. 754, 752, and 753; SEQ ID NOs. 755, 756, and 753; SEQ ID NOs. 755, 756, and 753; SEQ Sequence numbers 765, 752, and 753, Sequence numbers 766, 767, and 753, Sequence numbers 766, 768, and 753, Sequence numbers 769, 768, and 753, Sequence numbers 770, 767, and 753, Sequence numbers 765, 771, and 761, Sequence numbers 772, 771, and 761, Sequence numbers 774, 775, and 776, Sequence numbers 777, 778, and 776, Sequence numbers 779, 778, and 776, Sequence numbers 779, 780, and 776, Sequence numbers 777, 781, and 776, Sequence numbers 782, and 752 , and 753, SEQ ID NOs. 783, 752, and 753, SEQ ID NOs. 784, 785, and 753, SEQ ID NOs. 784, 786, and 753, SEQ ID NOs. 787, 786, and 753, SEQ ID NOs. 788, 785, and 753, SEQ ID NOs. 783, 789, and 761, SEQ ID NOs. 790, 789, and 761, SEQ ID NOs. 792, 793, and 794, SEQ ID NOs. 795, 796, and 794, SEQ ID NOs. 797, 796, and 794, SEQ ID NOs. 797, 798, and 794, or SEQ ID NOs. 795, 799, and 794.In some embodiments, the first antigen-binding domain is Fab that binds to CD3, and the second antigen-binding domain is HIV The scFv or CD4 EC domain that binds to gp120, wherein the first antigen-binding domain comprises a first HC and LC, and the second antigen-binding domain comprises a second HC, and the second HC, the first HC, and LC each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs. 751, 752, and 753, SEQ ID NOs. 754, 752, and 753, SEQ ID NOs. 755, 756, and 753, SEQ ID NOs. 755, 757, and 753, SEQ ID NOs. 758, 757, and 753, SEQ ID NOs. 759, 756, and 753, SEQ ID NOs. 764, 752, and 753, SEQ ID NOs. 765, 752, and 753, SEQ ID NOs. 766, 767, and 753, SEQ ID NOs. 766, 768, and 753, SEQ ID NOs. 769, 768, and 753, SEQ ID NOs. 770, 767, and 753, SEQ ID NOs. 777, 778, and 776, SEQ ID NOs. 779, 778, and 776, SEQ ID NOs. 779, 780, and 776, SEQ ID NOs. 777, 781, and 77 6. Sequence IDs 782, 752, and 753, 783, 752, and 753, 784, 785, and 753, 784, 786, and 753, 787, 786, and 753, 788, 785, and 753, 795, 796, and 794, 797, 796, and 794, 797, 798, and 794, or 795, 799, and 794.In some embodiments, the first antigen-binding domain is Fab that binds to CD3, and the second antigen-binding domain is HIV An EC domain of scFv or CD4 that binds to gp120, wherein the first antigen-binding domain comprises a first HC and LC, and the second antigen-binding domain comprises a second HC, and the second HC, the first HC, and LC each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs. 751, 752, and 753; SEQ ID NOs. 754, 752, and 753; SEQ ID NOs. 755, 756, and 753; SEQ ID NOs. 755, 757, and 753; SEQ ID NOs. 758, 757, and 753; or SEQ ID NOs. 759, 756, and 753. In some embodiments, the first antigen-binding domain is a Fab that binds to CD3, and the second antigen-binding domain is an EC domain of scFv or CD4 that binds to HIV gp120, the first antigen-binding domain comprises a first HC and LC, the second antigen-binding domain comprises a second HC, and the second HC, the first HC, and LC each comprise the amino acid sequence shown below, or each comprises an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs: 751, 752, and 753, or SEQ ID NOs: 755, 756, and 753.In some embodiments, the first antigen-binding domain is a Fab that binds to CD3, and the second antigen-binding domain is an EC domain of scFv or CD4 that binds to HIV gp120, the first antigen-binding domain comprises a first HC and LC, the second antigen-binding domain comprises a second HC, and the second HC, the first HC, and LC each comprise the amino acid sequence shown below, or each comprises an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs: 751, 752, and 753. In some embodiments, the first antigen-binding domain is a Fab that binds to CD3, and the second antigen-binding domain is an EC domain of scFv or CD4 that binds to HIV gp120, the first antigen-binding domain comprises a first HC and LC, the second antigen-binding domain comprises a second HC, and the second HC, the first HC, and LC each comprise the amino acid sequence shown below, or each comprises an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs: 755, 756, and 753.

[0019] Regarding further embodiments of multispecific (e.g., bispecific) antigen-binding molecules, in some embodiments, the multispecific antigen-binding molecule is a bispecific antigen-binding molecule. In some embodiments, the multispecific antigen-binding molecule binds to or targets human CD3 and HIV gp120. In some embodiments, the first VH and the first VL have sequence similarity of at least 80%, 81%, 82%, 83%, 84%, and 85% or more to human germline VH and human germline VL, respectively. In some embodiments, the first antigen-binding domain has reduced, minimal, or substantially no binding to protein A, or does not bind detectably to protein A. In some embodiments, the first antigen-binding domain is 10 -6 The bond equilibrium dissociation constant (K) greater than M D ) binds to protein A. In some embodiments, the first antigen-binding domain has a K content of less than 10 nM, for example, 9.5 nM, 9.0 nM, 8.5 nM, 8.0 nM, 7.5 nM, 7.0 nM, 6.5 nM, 6.0 nM, 5.5 nM, 5.0 nM, 4.5 nM, 4.0 nM, 3.5 nM, and less than 3.0 nM. D It binds to CD3. In some embodiments, the first antigen-binding domain has a K content of less than 3.0 nM (e.g., 2.5 nM). DIt binds to CD3. In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule has a serum half-life of at least 3 days, e.g., at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, or at least 16 days in humans or cynomolgus monkeys. In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule has a serum half-life of at least 7 days in humans or cynomolgus monkeys. In some embodiments, the multispecific (e.g., bispecific) antigen-binding molecule has a serum half-life of at least 7 days in humans. In some embodiments, the first antigen-binding domain has a K content of less than 7.0 nM, e.g., 6.5 nM, 6.0 nM, 5.5 nM, 5.0 nM, 4.5 nM, 4.0 nM, 3.5 nM, or less than 3.0 nM. D The multispecific (e.g., bispecific) antigen-binding molecule binds to CD3 and has a serum half-life of at least 5 days, e.g., at least 5.5 days, at least 6 days, at least 6.5 days, at least 7 days, at least 7.5 days, at least 8 days, at least 8.5 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, or at least 14 days in humans or cynomolgus monkeys. In some embodiments, the first antigen-binding domain has a K content of less than 3.0 nM (e.g., 2.5 nM). D The multispecific (e.g., bispecific) antigen-binding molecule binds to CD3 and has a serum half-life of at least 7 days in humans or cynomolgus monkeys. In some embodiments, the first antigen-binding domain has a K content of less than 3.0 nM (e.g., 2.5 nM). DThe multispecific (e.g., bispecific) antigen-binding molecule binds to CD3 and has a serum half-life of at least 7 days in humans. In some embodiments, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, and at least 90% of the N-linked glycosylation sites in at least one of the first VH, first VL, second VH, and second VL are sialylated. In some embodiments, the N-linked glycosylation sites in at least one of the first VH, first VL, second VH, and second VL have a sialic acid occupancy of at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, and at least 90% (e.g., a glycan containing one or two terminal sialic acid residues). In some embodiments, the sialylated N-linked glycosylation site in at least one of the first VH, first VL, second VH, and second VL contains 1 to 5 sialic acid residues, e.g., 1 to 4 sialic acid residues, e.g., 1 to 3 sialic acid residues, e.g., 1 to 2 sialic acid residues. In some embodiments, at least one of the first VH, first VL, second VH, and second VL is sialylated with N-acetylneuraminic acid (NANA). In some embodiments, the sialic acid residues exist in a bifurcated structure. In some embodiments, the sialic acid residues exist in a complex N-linked glycan structure. In some embodiments, the sialic acid residues exist in a hybrid N-linked glycan structure. In some embodiments, the glycan is terminally sialylated.

[0020] In another embodiment, a polynucleotide or a plurality of polynucleotides encoding at least a first VH and a first VL of a multispecific (e.g., bispecific) antigen-binding molecule is provided. In some embodiments, the polynucleotide(s) further comprises a polynucleotide or a plurality of polynucleotides encoding a second VH and a second VL of a multispecific (e.g., bispecific) antigen-binding molecule described herein. In some embodiments, the polynucleotide(s) comprises a polynucleotide or a plurality of polynucleotides encoding the HC of a first antigen-binding domain which is scFv, and the HC and LC of a second antigen-binding domain which is Fab, of a multispecific (e.g., bispecific) antigen-binding molecule described herein. In some embodiments, the polynucleotide(s) comprises a polynucleotide or a plurality of polynucleotides encoding the HC and LC of a first antigen-binding domain which is Fab, and the HC of a second antigen-binding domain which is scFv or the EC domain of CD4, of a multispecific (e.g., bispecific) antigen-binding molecule described herein. In some embodiments, the polynucleotide(s) may include a polynucleotide or a plurality of polynucleotides encoding the HC and LC of a first antigen-binding domain which is the Fab of a multispecific (e.g., bispecific) antigen-binding molecule, and the HC of a second antigen-binding domain which is the EC domain of CD4.In some embodiments, the polynucleotide(s) encodes a multispecific antigen-binding molecule described herein, comprising the following polynucleotide sequences, or polynucleotide sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the polynucleotide sequences shown below, respectively: SEQ ID NOs: 995, 996, and 997, SEQ ID NOs: 998, 999, and 1000, SEQ ID NO: 1 001, 1002, and 1003, sequence numbers 1004, 1005, and 1000, sequence numbers 1006, 1002, and 997, sequence numbers 1007, 1093, and 1000, sequence numbers 998, 1008, and 1000, sequence numbers 998, 1009, and 1000, sequence numbers 1010, 1011, and 1012, sequence numbers 1013, 1014, and 1015, sequence numbers 1016, 1017, and 1012, sequence numbers 1018, 1019, and 1012, sequence numbers 1018, 1020, and 1012, sequence numbers 1021, 1022, and 1023, or sequence numbers 1024, 1025, and 1023. In some embodiments, the polynucleotide(s) encodes a multispecific antigen-binding molecule described herein, each comprising a polynucleotide sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the polynucleotide sequence shown below: SEQ ID NOs: 995, 996, and 997. In some embodiments, the polynucleotide(s) encodes a multispecific antigen-binding molecule described herein, each comprising a polynucleotide sequence that is at least 95% (e.g., at least 96%, at least 97%, at least 98%, or at least 99%) identical to the shown polynucleotide sequence: SEQ ID NOs: 995, 996, and 997.In some embodiments, the polynucleotide(s) encodes a multispecific antigen-binding molecule described herein, comprising the following polynucleotide sequences: SEQ ID NOs: 995, 996, and 997. In some embodiments, the polynucleotide(s) encodes a multispecific antigen-binding molecule described herein, comprising a polynucleotide sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the polynucleotide sequence shown below: SEQ ID NOs: 998, 999, and 1000. In some embodiments, the polynucleotide(s) encodes a multispecific antigen-binding molecule described herein, comprising a polynucleotide sequence that is at least 95% (e.g., at least 96%, at least 97%, at least 98%, or at least 99%) identical to the shown polynucleotide sequence: SEQ ID NOs: 998, 999, and 1000. In some embodiments, the polynucleotide(s) encodes a multispecific antigen-binding molecule described herein, comprising the following polynucleotide sequences: SEQ ID NOs: 998, 999, and 1000. In some embodiments, the polynucleotide(s) are composed of DNA or RNA. In some embodiments, the polynucleotide(s) are composed of mRNA. In some embodiments, the polynucleotide(s) include codon bias for efficient expression in human cells. Further embodiments provide lipoplexes, such as lipid nanoparticles (LNPs), comprising the polynucleotide(s) described herein. This provides an expression cassette or a plurality of expression cassettes comprising one or more control sequences operably linked to a polynucleotide(s) as described herein.

[0021] In further embodiments, an expression vector or a plurality of expression vectors comprising one or more control sequences operably linked to a polynucleotide or expression cassette described herein is provided. In some embodiments, the expression vector includes a plasmid vector or a viral vector. In some embodiments, the expression vector comprises three, four, or five expression cassettes or cistrons. In some embodiments, the expression vector optionally comprises, in 5' to 3' order, (i) a first expression cassette or cistron comprising a first polynucleotide encoding an anti-HIV gp120 VL-light chain constant domain (CL) fusion protein, (ii) a second expression cassette or cistron comprising a second polynucleotide encoding an anti-HIV gp120 VH-Fc fusion protein, and (iii) a third expression cassette or cistron comprising a third polynucleotide encoding an anti-CD3 scFv-Fc fusion protein. In some embodiments, anti-HIV gp120 VL-CL fusion protein, anti-HIV gp120 VH-Fc fusion protein, and anti-CD3 Each scFv-Fc fusion protein contains the amino acid sequence shown below, or contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs. 802, 801, and 800; SEQ ID NOs. 802, 803, and 800; SEQ ID NOs. 802, 803, and 804; SEQ ID NOs. 802, 805 , and 804, Sequence IDs 802, 801, and 806, Sequence IDs 802, 803, and 806, Sequence IDs 802, 803, and 807, Sequence IDs 802, 805, and 807, Sequence IDs 802, 809, and 808, Sequence IDs 802, 810, and 808, Sequence IDs 802, 801, and 811, Sequence IDs 802, 809, and 812, Sequence IDs 802, 810, and 812, Sequence IDs 802, 805, and 813, Sequence IDs 802, 814, and 812, Sequence IDs 802, 801, and 815, Sequence IDs 802, 805, and 816, Sequence IDs 802, 801,and 817, Sequence IDs 802, 805, and 818, Sequence IDs 802, 810, and 819, Sequence IDs 802, 810, and 820, Sequence IDs 823, 822, and 821, Sequence IDs 823, 825, and 824, Sequence IDs 823, 825, and 826, Sequence IDs 823, 827, and 826, Sequence IDs 823, 829, and 828, Sequence IDs 823, 822, and 830, Sequence IDs 823, 825, and 830, Sequence IDs 823, 825, and 831, Sequence IDs 823, 827, and 831, Sequence IDs 823, 833, and 832, Sequence ID 823, 8 29, and 832, Sequence IDs 823, 827, and 834, Sequence IDs 823, 829, and 835, Sequence IDs 823, 829, and 836, Sequence IDs 823, 833, and 837, Sequence IDs 823, 838, and 837, Sequence IDs 823, 840, and 839, Sequence IDs 823, 829, and 841, Sequence IDs 823, 829, and 842, Sequence IDs 823, 829, and 843, Sequence IDs 823, 829, and 844, Sequence IDs 823, 829, and 845, Sequence IDs 823, 829, and 846, Sequence IDs 823, 833, and 846, Sequence ID 82 3, 838, and 846, Sequence numbers 823, 827, and 847, Sequence numbers 823, 829, and 848, Sequence numbers 823, 829, and 849, Sequence numbers 823, 829, and 850, Sequence numbers 823, 829, and 851, Sequence numbers 823, 829, and 852, Sequence numbers 823, 829, and 853, Sequence numbers 823, 829, and 854, Sequence numbers 823, 829, and 855, Sequence numbers 823, 829, and 856, Sequence numbers 823, 829, and 857, Sequence numbers 823, 829, and 858, Sequence numbers 823, 829, and 859, Sequence number Sequence numbers 823, 829, and 860, Sequence numbers 863, 862, and 861, Sequence numbers 863, 864, and 861, Sequence numbers 863, 864, and 865, Sequence numbers 863, 866, and 865, Sequence numbers 863, 868, and 867, Sequence numbers 863, 862, and 869, Sequence numbers 863, 864, and 869, Sequence numbers 863, 864, and 870, Sequence numbers 863, 866, and 870, Sequence numbers 863, 872, and 871, Sequence numbers 863, 868, and 871, Sequence numbers 863, 862, and 873, Sequence numbers 863, 866, and 874,Sequence numbers 863, 872, and 875, Sequence numbers 863, 868, and 875, Sequence numbers 863, 876, and 875, Sequence numbers 863, 862, and 877, Sequence numbers 863, 866, and 878, Sequence numbers 863, 862, and 879, Sequence numbers 863, 866, and 880, Sequence numbers 883, 882, and 881, Sequence numbers 883, 884, and 881, Sequence numbers 883, 884, and 885, Sequence numbers 883, 886, and 885, Sequence numbers 883, 888, and 887, Sequence numbers 883, 882, and 889, Sequence numbers 883, 884 , and 889, SEQ ID NOs: 883, 884, and 890, SEQ ID NOs: 883, 886, and 890, SEQ ID NOs: 883, 892, and 891, SEQ ID NOs: 883, 888, and 891, SEQ ID NOs: 883, 882, and 883, SEQ ID NOs: 883, 886, and 894, SEQ ID NOs: 883, 892, and 895, SEQ ID NOs: 883, 888, and 895, SEQ ID NOs: 883, 882, and 897, SEQ ID NOs: 883, 886, and 898, SEQ ID NOs: 883, 882, and 899, or SEQ ID NOs: 886 and 900. In some embodiments, the expression vector optionally comprises, in 5' to 3' order, (i) a first expression cassette or cistron containing a first polynucleotide encoding an anti-CD3 VL-CL fusion protein, (ii) a second expression cassette or cistron containing a second polynucleotide encoding an anti-CD3 VH-Fc fusion protein, and (iii) a third expression cassette or cistron containing a third polynucleotide encoding a CD4 extracellular (EC) domain-Fc fusion protein. In some embodiments, the anti-CD3 VL-CL fusion protein, the anti-CD3 VH-Fc fusion protein, and the anti-CD4 EC domain-Fc fusion protein each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: SEQ ID NOs: 753, 752, and 751, SEQ ID NOs: 753, 752, and 754,Sequence IDs 753, 756, and 755, Sequence IDs 753, 757, and 755, Sequence IDs 753, 757, and 758, Sequence IDs 753, 756, and 759, Sequence IDs 761, 760, and 754, Sequence IDs 761, 760, and 762, Sequence IDs 753, 763, and 751, Sequence IDs 753, 752, and 764, Sequence IDs 753, 752, and 765, Sequence IDs 753, 767, and 766, Sequence IDs 753, 768, and 766, Sequence IDs 753, 768, and 769, Sequence IDs 753, 767, and 770, Sequence IDs 761, 771, and 765, Sequence IDs 761, 771, and 772, Sequence IDs 776, 775, and 774, Sequence IDs 776, 77 8, and 777, SEQ ID NOs: 776, 778, and 779, SEQ ID NOs: 776, 780, and 779, SEQ ID NOs: 776, 781, and 777, SEQ ID NOs: 753, 752, and 782, SEQ ID NOs: 753, 752, and 783, SEQ ID NOs: 753, 785, and 784, SEQ ID NOs: 753, 786, and 784, SEQ ID NOs: 753, 786, and 787, SEQ ID NOs: 753, 785, and 788, SEQ ID NOs: 761, 789, and 783, SEQ ID NOs: 761, 789, and 790, SEQ ID NOs: 794, 793, and 792, SEQ ID NOs: 794, 796, and 795, SEQ ID NOs: 794, 796, and 797, SEQ ID NOs: 794, 798, and 797, or SEQ ID NOs: 794, 799, and 795. In some embodiments, anti-CD3 VL-CL fusion protein, anti-CD3 VH-Fc fusion protein, and anti-CD4, The EC domain-Fc fusion proteins each contain an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequences shown below: SEQ ID NOs. 753, 752, and 751. In some embodiments, the anti-CD3 VL-CL fusion protein, anti-CD3 VH-Fc fusion protein, and CD4 EC domain-Fc fusion protein each contain an amino acid sequence shown below: SEQ ID NOs. 753, 752, and 751. In some embodiments, the first, second, and third expression cassettes or cistrons each contain a promoter of the same or equivalent transcriptional strength, e.g., a constitutive promoter, e.g., a promoter selected from cytomegalovirus (CMV), SV40, RSV, EF1a, UBC, PGK, and CAGG. In some embodiments, the first, second, and third expression cassettes or cistrons include one or more promoters of different transcription intensities. In embodiments, the expression vector is a polynucleotide encoding a eukaryote-selective marker protein, such as glutamine synthetase (GS). The system further comprises a fourth expression cassette or cistron located at the 5' end of the first expression cassette or cistron, which contains a cydide. Generally, the fourth expression cassette or cistron, located at the 5' end of the first expression cassette and containing a polynucleotide encoding a eukaryote-selective marker protein, is translated from the same chain as the first, second, and third expression cassettes or cistrons.

[0022] In further embodiments, cells or cell populations are provided. In various embodiments, the cells or cell populations comprise polynucleotides of an expression cassette or multiple expression cassettes or expression vector(s) described herein. In some embodiments, the cells or cell populations comprise eukaryotic cells. In some embodiments, the cells or cell populations comprise mammalian cells, insect cells, plant cells, or yeast cells. In some embodiments, the mammalian cells are Chinese hamster ovary (CHO) cells. In some embodiments, the mammalian cells are human cells. In some embodiments, the cells are human fetal kidney cells. In some embodiments, the cells primarily sialylate the N-linked glycosylation sites within the variable domain (Fv) of the expressed antigen-binding molecule. In some embodiments, at least 50%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, and at least 95% or more of the N-linked glycosylation sites within the variable domain (Fv) of the expressed antigen-binding molecule are sialylated.

[0023] In further embodiments, pharmaceutical compositions are provided comprising one or more multispecific antigen-binding molecules described herein and a pharmaceutically acceptable carrier. In related embodiments, pharmaceutical compositions are provided comprising one or more multispecific antigen-binding molecules described herein, or one or more polynucleotides described herein that encode a lipoplex (e.g., LNP) described herein, and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition comprises an aqueous formulation. In some embodiments, the pharmaceutical composition contains one or more multispecific antigen-binding molecules described herein at concentrations of 0.1 mg / mL to 150 mg / mL, for example, 0.1 mg / mL to 100 mg / mL, for example, 1 mg / mL to 100 mg / mL, for example, 5 mg / mL to 60 mg / mL, for example, 20 mg / mL to 150 mg / mL, or 10 mg / mL to 50 mg / mL. In some embodiments, the pharmaceutical composition is lyophilized. In some embodiments, the pharmaceutical composition is formulated for intravenous, intramuscular, or subcutaneous administration. In some embodiments, the pharmaceutical composition further comprises a second agent for treating HIV infection. In some embodiments, the pharmaceutical composition comprises a Toll-like receptor (TLR) agonist or an IL-15 receptor agonist. The following further includes: In some embodiments, the pharmaceutical composition comprises a multispecific antigen-binding molecule having a first antigen-binding domain that binds to CD3 and a second antigen-binding domain that binds to the gp120 epitope or region of the CD4 binding site (CD4bs) and includes one or more extracellular (EC) domains of CD4, and optionally an IL-15 receptor agonist. In some embodiments, the one or more EC domains of CD4 include a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the sequence shown in SEQ ID NOs. 746-749, or the amino acid sequence of SEQ ID NOs. 746-749 (e.g., SEQ ID NO. 746). In some embodiments, the C domain of CD4 contains a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99% identical to the sequence of sequence number 746. In some embodiments, the EC domain of CD4 contains a sequence that is at least 95% identical to the sequence of sequence number 746. In some embodiments, the EC domain of CD4 contains a sequence that is at least 99% identical to the sequence of sequence number 746. In some embodiments, the EC domain of CD4 contains the sequence of sequence number 746.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 11, 8, 4, 9, and 10, or SEQ ID NOs: 1, 12, 8, 4, 9, and 10, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746), or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 12, 8, 4, 9, and 10, and the second antigen-binding domain comprises one EC domain of CD4 containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the CD4 EC domain of SEQ ID NO: 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 12, 8, 4, 9, and 10, respectively, and the second antigen-binding domain comprises one EC domain of CD4, each containing an amino acid sequence that is at least 95% identical to the CD4 EC domain of SEQ ID NO: 746.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 12, 8, 4, 9, and 10, respectively, and the second antigen-binding domain comprises one EC domain of CD4, each containing an amino acid sequence that is at least 99% identical to the CD4 EC domain of SEQ ID NO: 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 12, 8, 4, 9, and 10, respectively, and the second antigen-binding domain comprises one EC domain of CD4 containing the amino acid sequence of SEQ ID NO: 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Chothia): SEQ ID NOs: 17, 18, 23, 20, 24, and 25, respectively, and the second antigen-binding domain is a CD4 selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746). The CD4 contains an EC domain, or one or more EC domains of CD4 containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Chothia): SEQ ID NOs: 17, 18, 23, 20, 24, and 25, and the second antigen-binding domain comprises one EC domain of CD4, each containing an amino acid sequence that is at least 95% (e.g., at least 96%, at least 97%, at least 98%, or at least 99%) identical to the CD4 EC domain of SEQ ID NO: 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Chothia): SEQ ID NOs: 17, 18, 23, 20, 24, and 25, respectively, and the second antigen-binding domain comprises one EC domain of CD4 containing the amino acid sequence of SEQ ID NO: 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10, respectively, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746 to 749 (e.g., SEQ ID NO. 746), or one or more CD4 EC domains comprising amino acid sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10, respectively, and the second antigen-binding domain comprises one EC domain of CD4, each containing an amino acid sequence that is at least 95% (e.g., at least 96%, at least 97%, at least 98%, or at least 99%) identical to the CD4 EC domain of SEQ ID NO. 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10, respectively, and the second antigen-binding domain comprises one EC domain of CD4 containing the amino acid sequence of SEQ ID NO. 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 42, 40, 37, 41, and 25, or SEQ ID NOs: 34, 43, 40, 37, 41, and 25, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746), or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 43, 40, 37, 41, and 25, respectively, and the second antigen-binding domain comprises the CD4 EC domain of SEQ ID NO: 746, or one EC domain of CD4 comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 43, 40, 37, 41, and 25, respectively, and the second antigen-binding domain comprises one EC domain of CD4, comprising an amino acid sequence that is at least 95% (e.g., at least 96%, at least 97%, at least 98%, or at least 99%) identical to the CD4 EC domain of SEQ ID NO: 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 43, 40, 37, 41, and 25, respectively, and the second antigen-binding domain comprises one EC domain of CD4 containing the amino acid sequence of SEQ ID NO: 746.In some embodiments, the first antigen-binding domain comprises a first VH and a first VL, each containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequences: SEQ ID NOs: 49 and 55, SEQ ID NOs: 50 and 55, SEQ ID NOs: 50 and 56, SEQ ID NOs: 51 and 55, or SEQ ID NOs: 51 and 56, and the second antigen-binding domain is CD4 selected from the group consisting of SEQ ID NOs: 746 to 749 (e.g., SEQ ID NO: 746). The composition comprises one or more EC domains of CD4, which include an EC domain or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the TLR agonist is a TLR2 agonist, a TLR3 agonist, a TLR7 agonist, a TLR8 agonist, or a TLR9 agonist. In some embodiments, the pharmaceutical composition further comprises a TLR7 agonist selected from the group consisting of besatrimod, imiquimod, and reximod. In some embodiments, the pharmaceutical composition comprises a first multispecific antigen-binding molecule and a second or additional antigen-binding molecule, the first multispecific antigen-binding molecule and the second or additional antigen-binding molecule binding to different epitopes or regions of gp120 selected from the group consisting of (i) a third variable loop (V3) containing N332 oligomannose glycan (e.g., a high-mannose patch), (ii) a second variable loop (V2) (e.g., an Env trimer vertex), (iii) a CD4 binding site (CD4bs), (iv) a gp120 / gp41 interface, or (v) a silent surface of gp120. In some embodiments, the first multispecific antigen-binding molecule binds to a third variable loop (V3) containing N332 oligomannose glycan (e.g., a high-mannose patch), and the second or additional antigen-binding molecule binds to a CD4 binding site (CD4bs).In some embodiments, the first multispecific antigen-binding molecule is GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-125, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, PGT-136, PGT-137, PGT-138, PGT-139, 10-1074, 10-1074-J, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG4 2, Competing with or containing the VH and VL regions of antibodies selected from the group consisting of 354BG33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03, the second or additional antigen-binding molecule is GS-9723, GS-5423, 3BNC117, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, VRC06b01 Competing with or containing the VH and VL regions derived from antibodies selected from the group consisting of VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25. In some embodiments, the first multispecific antigen-binding molecule competes with or includes VH and VL regions derived from an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134, and the second or additional antigen-binding molecule competes with or includes VH and VL regions derived from an antibody selected from the group consisting of GS-9723, GS-5423, 3BNC117, VRC07, and VRC07-523.In some embodiments, the first multispecific antigen-binding molecule competes with or includes the VH and VL regions of an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134, and the second or additional antigen-binding molecule includes the EC domain of CD4. In some embodiments, the first multispecific antigen-binding molecule binds to a CD4 binding site (CD4bs), and the second or additional antigen-binding molecule binds to a third variable loop (V3) (e.g., a high-mannose patch) containing N332 oligomannose glycan. In some embodiments, the first multispecific antigen-binding molecule is GS-9723, GS-5423, 3BNC117, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, VRC06b01 The second or additional antigen-binding molecule competes with or includes the VH and VL regions of antibodies selected from the group consisting of VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25, and the second or additional antigen-binding molecule is GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-1 25, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, PGT-136, PGT-137, PGT-1 38, PGT-139, 10-1074, 10-1074-J, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG42, 354BG Competing with or containing the VH and VL regions derived from antibodies selected from the group consisting of 33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03.In some embodiments, the first multispecific antigen-binding molecule competes with or includes VH and VL regions derived from an antibody selected from the group consisting of GS-9723, GS-5423, 3BNC117, VRC07, and VRC07-523, and the second or additional antigen-binding molecule competes with or includes VH and VL regions derived from an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134. In some embodiments, the first multispecific antigen-binding molecule competes with or includes the EC domain of CD4, and the second or additional antigen-binding molecule is GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-125, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, PGT-136, PGT-137, PG Competing with or containing the VH and VL regions derived from antibodies selected from the group consisting of T-138, PGT-139, 10-1074, 10-1074-J, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG42, 354BG33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03. In some embodiments, the first multispecific antigen-binding molecule competes with or includes the EC domain of CD4, and the second or additional antigen-binding molecule competes with or includes the VH and VL regions of an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134.In some embodiments, the pharmaceutical composition further comprises additional antigen-binding molecules that compete with or contain the VH and VL regions derived from antibodies selected from the group consisting of GS-9723, GS-5423, 3BNC117, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, VRC06b01, VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25. In some embodiments, the pharmaceutical composition further comprises additional antigen-binding molecules that compete with or contain VH and VL regions derived from an antibody selected from the group consisting of GS-9723, GS-5423, 3BNC117, VRC07, and VRC07-523. In some embodiments, the pharmaceutical composition comprises (i) a multispecific (e.g., bispecific) antigen-binding molecule comprising the EC domain of CD4 as described herein; (ii) an antibody or multispecific antigen-binding molecule that competes with or includes the VH and VL regions derived from an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134; and (iii) an antibody or multispecific antigen-binding molecule that competes with or includes the VH and VL regions derived from an antibody selected from the group consisting of GS-9723, GS-5423, 3BNC117, VRC07, and VRC07-523. In some embodiments, the pharmaceutical composition includes additional multispecific antigen-binding molecules that compete with or include the VH and VL regions derived from the antibody that bind to the second variable loop (V2) of gp120 (e.g., the Env trimer apex).In some embodiments, the pharmaceutical composition competes with or is equivalent to the VH and VL regions derived from antibodies selected from the group consisting of PG9, PG16, PGC14, PGG14, PGT-142, PGT-143, PGT-144, PGT-145, CH01, CH59, PGDM1400, CAP256, CAP256-VRC26.08, CAP256-VRC26.09, CAP256-VRC26.25, PCT64-24E, and VRC38.01. The pharmaceutical composition includes additional multispecific antigen-binding molecules. In some embodiments, the pharmaceutical composition includes additional multispecific antigen-binding molecules that compete with or include antibody-derived VH and VL regions that bind to the gp120 / gp41 interface. In some embodiments, the pharmaceutical composition includes additional multispecific antigen-binding molecules that compete with or include antibody-derived VH and VL regions selected from the group consisting of PGT-151, CAP248-2B, 35O22, 8ANC195, ACS202, VRC34, and VRC34.01. In some embodiments, the pharmaceutical composition includes additional multispecific antigen-binding molecules that compete with or include antibody-derived VH and VL regions that bind to the epitope or region of gp41 in the membrane proximal region (MPER). In some embodiments, the pharmaceutical composition includes additional multispecific antigen-binding molecules that compete with or include VH and VL regions derived from an antibody selected from the group consisting of 10E8, 10E8v4, 10E8-5R-100cF, 4E10, DH511.11P, 2F5, 7b2, and LN01. In some embodiments, the pharmaceutical composition includes an additional antigen-binding molecule or antigen-binding fragment thereof that performs at least one of binding to HIV, inhibiting it, and neutralizing it, or a polynucleotide encoding an additional antigen-binding molecule or antigen-binding fragment thereof, wherein the additional antigen-binding molecule or antigen-binding fragment does not compete with one or more multispecific antigen-binding molecules for binding to gp120.

[0024] In further embodiments, kits are provided comprising one or more containers containing one or more of the multispecific (e.g., bispecific) antigen-binding molecules, polynucleotides(or polynucleotides), lipoplexes(e.g., LNPs), or pharmaceutical compositions described herein. In some embodiments, the kit contains one or more multispecific antigen-binding molecules or polynucleotides(or polynucleotides) in one or more unit doses in one or more containers (e.g., one or more vials, ampoules, or syringes). In some embodiments, the kit contains one or more multispecific antigen-binding molecules in one or more unit doses and a second agent for treating HIV infection in a separate container. In some embodiments, the kit further comprises at least one of a Toll-like receptor (TLR) agonist and an IL-15 receptor agonist. In some embodiments, the kit comprises a multispecific antigen-binding molecule having a first antigen-binding domain that binds to CD3 and a second antigen-binding domain that binds to the gp120 epitope or region of the CD4 binding site (CD4bs) and includes one or more extracellular (EC) domains of CD4, and optionally an IL-15 receptor agonist. In some embodiments, the one or more EC domains of CD4 include a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the sequence shown in SEQ ID NOs. 746-749 (e.g., SEQ ID NO. 746), or the amino acid sequence of SEQ ID NOs. In some embodiments, the C domain of CD4 contains a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99% identical to the sequence of sequence number 746. In some embodiments, the EC domain of CD4 contains a sequence that is at least 95% identical to the sequence of sequence number 746. In some embodiments, the EC domain of CD4 contains a sequence that is at least 99% identical to the sequence of sequence number 746.In some embodiments, the EC domain of CD4 includes the sequence of sequence number 746. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 11, 8, 4, 9, and 10, or SEQ ID NOs: 1, 12, 8, 4, 9, and 10, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746), or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Chothia): SEQ ID NOs. 17, 18, 23, 20, 24, and 25, respectively, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746 to 749 (e.g., SEQ ID NO. 746), or one or more CD4 EC domains comprising amino acid sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10, respectively, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746 to 749 (e.g., SEQ ID NO. 746), or one or more CD4 EC domains comprising amino acid sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 42, 40, 37, 41, and 25, or SEQ ID NOs: 34, 43, 40, 37, 41, and 25, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746), or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH and a first VL, each containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequences: SEQ ID NOs: 49 and 55, SEQ ID NOs: 50 and 55, SEQ ID NOs: 50 and 56, SEQ ID NOs: 51 and 55, or SEQ ID NOs: 51 and 56, and the second antigen-binding domain comprises a CD4 selected from the group consisting of SEQ ID NOs: 746 to 749 (e.g., SEQ ID NO: 746). The TLR agonist comprises one or more EC domains of CD4, which include an EC domain or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the TLR agonist is a TLR2 agonist, a TLR3 agonist, a TLR7 agonist, a TLR8 agonist, or a TLR9 agonist. In some embodiments, the TLR7 agonist is selected from the group consisting of besatrimod, imiquimod, and reximod. In some embodiments, the kit comprises a first multispecific antigen-binding molecule and a second or additional antigen-binding molecule, the first multispecific antigen-binding molecule and the second or additional antigen-binding molecule binding to different epitopes or regions of gp120 selected from the group consisting of (i) a third variable loop (V3) containing N332 oligomannose glycan (e.g., a high-mannose patch), (ii) a second variable loop (V2) (e.g., an Env trimer vertex), (iii) a CD4 binding site (CD4bs), (iv) a gp120 / gp41 interface, or (v) a silent surface of gp120. In some embodiments, the first multispecific antigen-binding molecule binds to a third variable loop (V3) containing N332 oligomannose glycan (e.g., a high-mannose patch), and the second or additional antigen-binding molecule binds to a CD4 binding site (CD4bs).In some embodiments, the first multispecific antigen-binding molecule is GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-125, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, PGT-136, PGT-137, PGT-138, PGT-139, 10-1074, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG42, 354 The second or additional antigen-binding molecule competes with or includes the VH and VL regions of antibodies selected from the group consisting of BG33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03, and the second or additional antigen-binding molecule is GS-9723, GS-5423, 3BNC117, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, VRC06b01 Competing with or containing the VH and VL regions derived from antibodies selected from the group consisting of VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25. In some embodiments, the first multispecific antigen-binding molecule competes with or includes VH and VL regions derived from an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134, and the second or additional antigen-binding molecule competes with or includes VH and VL regions derived from an antibody selected from the group consisting of GS-9723, GS-5423, 3BNC117, VRC07, and VRC07-523.In some embodiments, the first multispecific antigen-binding molecule competes with or includes the VH and VL regions of an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722, and PGT-121, and the second or additional antigen-binding molecule includes the EC domain of CD4. In some embodiments, the first multispecific antigen-binding molecule binds to a CD4 binding site (CD4bs), and the second or additional antigen-binding molecule binds to a third variable loop (V3) (e.g., a high-mannose patch) containing N332 oligomannose glycan. In some embodiments, the first multispecific antigen-binding molecule is GS-9723, GS-5423, 3BNC117, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, VRC06b01. The second or additional antigen-binding molecule competes with or includes the VH and VL regions of antibodies selected from the group consisting of VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25, and the second or additional antigen-binding molecule is GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, Competes with or contains the VH and VL regions derived from antibodies selected from the group consisting of PGT-125, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, PGT-136, PGT-137, PGT-138, PGT-139, 10-1074, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG42, 354BG33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03. In some embodiments, the first multispecific antigen-binding molecule competes with or includes VH and VL regions derived from an antibody selected from the group consisting of GS-9723, GS-5423, 3BNC117, VRC07, and VRC07-523, and the second or additional antigen-binding molecule competes with or includes VH and VL regions derived from an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134.In some embodiments, the first multispecific antigen-binding molecule competes with or includes the EC domain of CD4, and the second or additional antigen-binding molecule is GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-125, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, PGT-136, PGT-1 Competing with or containing the VH and VL regions derived from antibodies selected from the group consisting of 37, PGT-138, PGT-139, 10-1074, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG42, 354BG33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03. In some embodiments, the first multispecific antigen-binding molecule competes with or includes the EC domain of CD4, and the second or additional antigen-binding molecule competes with or includes the VH and VL regions of an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134. In some embodiments, the kit further comprises a second or additional antigen-binding molecule that competes with or includes the VH and VL regions derived from antibodies selected from the group consisting of GS-9723, GS-5423, 3BNC117, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, VRC06b01, VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25.In some embodiments, the kit further comprises a second or additional antigen-binding molecule that competes with or includes the VH and VL regions of an antibody selected from the group consisting of GS-9723, GS-5423, 3BNC117, VRC07, and VRC07-523. In some embodiments, the kit comprises (i) a multispecific antigen-binding molecule containing the EC domain of CD4 as described herein, (ii) an antibody or multispecific antigen-binding molecule that competes with or contains the VH and VL regions of an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134, and (iii) an antibody or multispecific antigen-binding molecule that competes with or contains the VH and VL regions of an antibody selected from the group consisting of GS-9723, GS-5423, 3BNC117, VRC07, and VRC07-523. In some embodiments, the kit comprises two or more unit doses, which may be the same or different.

[0025] In further embodiments, methods for producing multispecific (e.g., bispecific) antigen-binding molecules described herein are provided. In some embodiments, the production method comprises (a) culturing cells or cell populations described herein, transformed with polynucleotides(or polynucleotides) or expression cassettes(or expression cassettes) described herein, in a cell culture under conditions sufficient to express multispecific antigen-binding molecules; and (b) isolating or purifying the antigen-binding molecules from the cell culture. In some embodiments, the first antigen-binding domain is scFv and the second antigen-binding domain is Fab. In some embodiments, the first antigen-binding domain is Fab and the second antigen-binding domain is the EC domain of Fab or CD4. In some embodiments, the first antigen-binding domain is Fab and the second antigen-binding domain is the EC domain of CD4. In some embodiments, the polypeptide containing the first antigen-binding domain and the polypeptide containing the second antigen-binding domain are expressed and assembled in the same cell. In some embodiments, the isolation or purification step includes protein A affinity chromatography. In some embodiments, at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more of the multispecific antigen-binding molecules are isolated or purified. In some embodiments, the isolation or purification step further includes ion exchange chromatography. In some embodiments, at least 95%, 96%, 97%, 98%, or 99% or more of the multispecific antigen-binding molecules are isolated or purified. In some embodiments, when determined using size exclusion chromatography (SEC), the multispecific antigens At least 95%, 96%, 97%, 98%, and 99% or more of the proto-binding molecules are isolated or purified as non-aggregating soluble heterodimers. In some embodiments, the isolated or purified multispecific antigen-binding molecules, when evaluated by analytical ion-exchange chromatography, exhibit increased homogeneity, with the integrated area of ​​the main peak representing the unmodified target species being at least 95%, 96%, 97%, and 98% or more of the total integrated protein peak area. In some embodiments, the isolated or purified antigen-binding molecules have less than 35%, 30%, 25%, 20%, 15%, 10%, 9%, 8%, and 7% acidic contaminants. In some embodiments, cells or cell populations are cultured in a culture volume of at least 2 L, for example, at least 5 L, 10 L, 50 L, 100 L, 150 L, 200 L, and 250 L or more. In some embodiments, the method further comprises formulating the antigen-binding molecules into a sterile pharmaceutical composition suitable for administration to human subjects.

[0026] In another embodiment, a method is provided for treating or preventing HIV in a human subject who requires such treatment or prevention. In some embodiments, the method comprises administering to a subject an effective amount of one or more multispecific (e.g., bispecific) antigen-binding molecules or pharmaceutical compositions described herein. In related embodiments, a method is provided for preventing or treating HIV infection or HIV-related disease. In some embodiments, the method comprises the steps of identifying a patient who requires such prevention or treatment, and administering to the patient a therapeutically effective amount of a first therapeutic agent comprising at least one multispecific (e.g., bispecific) antigen-binding molecule or pharmaceutical composition described herein. In some embodiments, the method further comprises administering to a subject a second agent for treating HIV infection. In some embodiments, the subject is receiving antiretroviral therapy (ART). ) are not being received, or ART is discontinued before administration of one or more multispecific antigen-binding molecules. In some embodiments, ART is discontinued after one or more administrations of one or more multispecific antigen-binding molecules. In some embodiments, the method further comprises administering one or more antiretroviral therapy (ART) agents as the target. In some embodiments, the method further comprises administering at least one of a TLR agonist and an IL-15 receptor agonist as the target. In some embodiments, the method comprises administering a multispecific antigen-binding molecule having a first antigen-binding domain that binds to CD3, and a second antigen-binding domain that binds to the gp120 epitope or region of the CD4 binding site (CD4bs) and includes one or more extracellular (EC) domains of CD4, and optionally an IL-15 receptor agonist. In some embodiments, one or more EC domains of CD4 include a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the sequence shown in SEQ ID NOs. 746-749 (e.g., SEQ ID NOs. 746). In some embodiments, the C domain of CD4 includes a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99% identical to the sequence of SEQ ID NOs. In some embodiments, the EC domain of CD4 includes a sequence that is at least 95% identical to the sequence of SEQ ID NOs. 746. In some embodiments, the EC domain of CD4 includes a sequence that is at least 99% identical to the sequence of sequence number 746.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 11, 8, 4, 9, and 10, or SEQ ID NOs: 1, 12, 8, 4, 9, and 10, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746), or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Chothia): SEQ ID NOs. 17, 18, 23, 20, 24, and 25, respectively, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746 to 749 (e.g., SEQ ID NO. 746), or one or more CD4 EC domains comprising amino acid sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10, respectively, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746 to 749 (e.g., SEQ ID NO. 746), or one or more CD4 EC domains comprising amino acid sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 42, 40, 37, 41, and 25, or SEQ ID NOs: 34, 43, 40, 37, 41, and 25, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746), or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH and a first VL, each containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequences: SEQ ID NOs: 49 and 55, SEQ ID NOs: 50 and 55, SEQ ID NOs: 50 and 56, SEQ ID NOs: 51 and 55, or SEQ ID NOs: 51 and 56, and the second antigen-binding domain comprises a CD4 selected from the group consisting of SEQ ID NOs: 746 to 749 (e.g., SEQ ID NO: 746). The TLR agonist comprises one or more EC domains of CD4, which include an EC domain or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the TLR agonist is a TLR2 agonist, a TLR3 agonist, a TLR7 agonist, a TLR8 agonist, or a TLR9 agonist. In some embodiments, the TLR7 agonist is selected from the group consisting of besatrimod, imiquimod, and reximod. In some embodiments, the method comprises administering a first multispecific antigen-binding molecule and a second or additional antigen-binding molecule, the first multispecific antigen-binding molecule and the second or additional antigen-binding molecule binding to different epitopes or regions of gp120 selected from the group consisting of (i) a third variable loop (V3) containing N332 oligomannose glycan (e.g., a high-mannose patch), (ii) a second variable loop (V2) (e.g., an Env trimer vertex), (iii) a CD4 binding site (CD4bs), (iv) a gp120 / gp41 interface, or (v) a silent surface of gp120. In some embodiments, the first multispecific antigen-binding molecule binds to a third variable loop (V3) containing N332 oligomannose glycan (e.g., a high-mannose patch), and the second or additional antigen-binding molecule binds to a CD4 binding site (CD4bs).In some embodiments, the first multispecific antigen-binding molecule is 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-125, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, PGT-136, PGT-137, PGT-138, PGT-139, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG4 2, Competing with or containing the VH and VL regions of antibodies selected from the group consisting of 354BG33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03, the second or additional antigen-binding molecule is GS-9723, GS-5423, 3BNC117, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, VRC06b01 Competing with or containing the VH and VL regions derived from antibodies selected from the group consisting of VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25. In some embodiments, the first multispecific antigen-binding molecule competes with or includes VH and VL regions derived from an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134, and the second or additional antigen-binding molecule competes with or includes VH and VL regions derived from GS-9723, GS-5423, 3BNC117, VRC07, and VRC07-523.In some embodiments, the first multispecific antigen-binding molecule competes with or includes the VH and VL regions of an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134, and the second or additional antigen-binding molecule includes the EC domain of CD4. In some embodiments, the first multispecific antigen-binding molecule binds to a CD4 binding site (CD4bs), and the second or additional antigen-binding molecule binds to a third variable loop (V3) (e.g., a high-mannose patch) containing N332 oligomannose glycan. In some embodiments, the first multispecific antigen-binding molecule competes with or includes the VH and VL regions derived from antibodies selected from the group consisting of GS-9723, GS-5423, 3BNC117, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, VRC06b01, VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25, and a second or additional antigen-binding molecule. The molecules are GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-125, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, PGT-136, PGT-137, PGT-138, PGT-139, 10-1074, 10-1074-J, VRC24, 2G12, and B. Competing with or containing the VH and VL regions derived from antibodies selected from the group consisting of G18, 354BG8, 354BG18, 354BG42, 354BG33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03. In some embodiments, the first multispecific antigen-binding molecule competes with or includes VH and VL regions derived from an antibody selected from the group consisting of GS-9723, GS-5423, 3BNC117, VRC07, and VRC07-523, and the second or additional antigen-binding molecule competes with or includes VH and VL regions derived from 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134. In some embodiments, the first multispecific antigen-binding molecule competes with or includes the EC domain of CD4, and the second or additional antigen-binding molecule is GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-125, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, PGT-136, PGT-137, PG Competing with or containing the VH and VL regions derived from antibodies selected from the group consisting of T-138, PGT-139, 10-1074, 10-1074-J, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG42, 354BG33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03.In some embodiments, the first multispecific antigen-binding molecule competes with or includes the EC domain of CD4, and the second or additional antigen-binding molecule competes with or includes the VH and VL regions of an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134. In some embodiments, the method further comprises administering a second or additional antigen-binding molecule that competes with or includes the VH and VL regions derived from antibodies selected from the group consisting of GS-9723, GS-5423, 3BNC117, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, VRC06b01, VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25. In some embodiments, the method further comprises administering a second or additional antigen-binding molecule that competes with or includes the VH and VL regions of an antibody selected from the group consisting of GS-9723, GS-5423, 3BNC117, VRC07, and VRC07-523. In some embodiments, the method comprises co-administration of (i) a multispecific antigen-binding molecule comprising the EC domain of CD4 as described herein, (ii) an antibody or multispecific antigen-binding molecule that competes with or contains VH and VL regions derived from an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134, and (iii) an antibody or multispecific antigen-binding molecule that competes with or contains VH and VL regions derived from an antibody selected from the group consisting of GS-9723, GS-5423, 3BNC117, VRC07, and VRC07-523.In some embodiments, the method further includes administering to a human subject an additional antigen-binding molecule or its antigen-binding fragment that performs at least one of binding to HIV, inhibiting it, and neutralizing it, or a polynucleotide encoding an additional antigen-binding molecule or its antigen-binding fragment. In some embodiments, the method involves administering an antibody or polyspecific antigen-binding molecule that competes with or contains the VH and VL regions that bind to the third variable loop (V3) of gp120 (e.g., high-mannose patch) containing N332 oligomannose glycan, the human subject being the following amino acid residues: N332glycan, D325, and T63; N332glycan, D325, and L179; N332glycan, D325, and T320; N332glycan, D325, and H330; N332glycan, D325, T63, and L179; N332glycan, D325, T63, and T320; N332glycan, D325, T63, and The individual is infected with HIV expressing gp120 containing H330;N332glycan, D325, L179, and T320;N332glycan, D325, L179, and H330;N332glycan, D325, T320, and H330;N332glycan, D325, T63, T320, and H330;N332glycan, D325, T63, L179, and T320;N332glycan, D325, T63, L179, and H330;N332glycan, D325, L179, T320, and H330; or N332glycan, D325, T63, L179, T320, and H330, with the location and residues based on SEQ ID NO: 69. In some embodiments, the method comprises administering an antibody or a multispecific antigen-binding molecule that competes with or contains the VH and VL regions that bind to the CD4 binding site of gp120, wherein the human subject is infected with HIV expressing gp120 containing the following amino acid residues: I201 and F353, I201, I108 and F353, I201, I108, A281 and F353; I201, E102, I108, A281 and F353; or I201, E102, I108, A281, Y318 and F353, with the location and residues relative to SEQ ID NO: 73.In some embodiments, the method involves administering one or more multispecific antigen-binding molecules, optionally together with a TLR agonist or an IL-15 receptor agonist, multiple times at predetermined intervals. In some embodiments, the method involves administering a multispecific antigen-binding molecule having a first antigen-binding domain that binds to CD3 and a second antigen-binding domain that binds to the gp120 epitope or region of the CD4 binding site (CD4bs) and includes one or more extracellular (EC) domains of CD4, and optionally an IL-15 receptor agonist, wherein the multispecific antigen-binding molecule and the IL-15 receptor agonist are administered independently at predetermined intervals. In some embodiments, one or more EC domains of CD4 include a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the sequence shown in SEQ ID NOs. 746-749, or the amino acid sequence of SEQ ID NOs. 746-749 (e.g., SEQ ID NO. 746). In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 11, 8, 4, 9, and 10, or SEQ ID NOs: 1, 12, 8, 4, 9, and 10, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746), or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Chothia): SEQ ID NOs. 17, 18, 23, 20, 24, and 25, respectively, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746 to 749 (e.g., SEQ ID NO. 746), or one or more CD4 EC domains comprising amino acid sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10, respectively, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746 to 749 (e.g., SEQ ID NO. 746), or one or more CD4 EC domains comprising amino acid sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 42, 40, 37, 41, and 25, or SEQ ID NOs: 34, 43, 40, 37, 41, and 25, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746), or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH and a first VL, each comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequences: SEQ ID NOs: 49 and 55, SEQ ID NOs: 50 and 55, SEQ ID NOs: 50 and 56, SEQ ID NOs: 51 and 55, or SEQ ID NOs: 51 and 56, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746 to 749 (e.g., SEQ ID NO: 746), or at least 80% identical thereto. The EC domains of CD4 include one or more amino acid sequences that are 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical. In some embodiments, the subjects are chronically infected with HIV. In some embodiments, one or more multispecific antigen-binding molecules, polynucleotides, vectors, LNPs, and / or pharmaceutical compositions are administered systemically or topically. In some embodiments, one or more multispecific antigen-binding molecules, polynucleotides, vectors, LNPs, and / or pharmaceutical compositions are administered via a route selected from intravenous, subcutaneous, intramuscular, intradermal, and mucosal (e.g., oral, nasal, rectal, vaginal) routes. In some embodiments, one or more multispecific antigen-binding molecules, polynucleotides, vectors, LNPs, and / or pharmaceutical compositions, as well as one or more additional therapeutic agents, are administered via the same route of administration. In some embodiments, one or more multispecific antigen-binding molecules, polynucleotides, vectors, LNPs, and / or pharmaceutical compositions, and one or more additional therapeutic agents are administered by different routes of administration. In some embodiments, one or more multispecific antigen-binding molecules, polynucleotides, vectors, LNPs, and / or pharmaceutical compositions, and one or more additional therapeutic agents are co-administered according to the same schedule (e.g., co-administered at the same time intervals). In some embodiments, one or more multispecific antigen-binding molecules, polynucleotides, vectors, LNPs, and / or pharmaceutical compositions, and one or more additional therapeutic agents are co-administered according to different schedules (e.g., co-administered at different time intervals).In some embodiments, one or more multispecific antigen-binding molecules, polynucleotides, vectors, LNPs, and / or pharmaceutical compositions are administered in doses of 1 μg / kg to 5 μg / kg, e.g., 350 μg / kg to 550 μg / kg, e.g., 0.3 mg / kg to 30 mg / kg, e.g., 2 mg / kg to 10 mg / kg, e.g., 1 μg / kg to a maximum of 2 μg / kg, 3 μg / kg, 4 μg / kg, 5 μg / kg, 10 μg / kg, 50 μg / kg, 100 μg / kg, 250 μg / kg, 300 μg / kg, 350 μg / kg, 400 μg / kg, 410 μg / kg, 420 μg / kg, 43 μg / kg, and 43 μg / kg. It is administered in doses within the range of 0 μg / kg, 440 μg / kg, 450 μg / kg, 460 μg / kg, 470 μg / kg, 480 μg / kg, 490 μg / kg, 500 μg / kg, 750 μg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 3.5 mg / kg, 4 mg / kg, 4.5 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, or 50 mg / kg body weight. In some embodiments, one or more multispecific antigen-binding molecules, polynucleotides, vectors, LNPs, and / or pharmaceutical compositions are administered in doses of 0.05 mg to 1000 mg, for example, 0.05 mg to 150 mg, for example, 0.05 mg to 0.35 mg, for example, 25 mg to 50 mg, for example, 30 mg to 35 mg, for example, 10 mg to 1000 mg, for example, 50 mg to 1000 mg, for example, per dose The dosage is 100 mg to 700 mg, for example, at least 0.05 mg to a maximum of 0.1 mg, 0.2 mg, 0.3 mg, 0.35 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 1.0 mg, 5 mg, 10 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg per dose.In some embodiments, the method involves administering one or more multispecific antigen-binding molecules, polynucleotides, vectors, LNPs, and / or pharmaceutical compositions, along with one or more optional additional therapeutic agents, multiple times at predetermined intervals. In some embodiments, the method involves administering over a period of at least approximately 2 weeks, 3 weeks, 1 month, 6 weeks, 2 months, 10 weeks, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, or 24 months or longer. In some embodiments, the method involves administering one or more doses at predetermined intervals with at least 1 week and at least 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months apart. In some embodiments, the method involves administering one or more multispecific antigen-binding molecules, polynucleotides, vectors, LNPs, and / or pharmaceutical compositions once weekly (i.e., QW), every other week (i.e., once every two weeks, or Q2W), every three weeks (i.e., once every three weeks, or Q3W), once a month (i.e., QM), or every other month (i.e., once every month, or once every two months, or Q2M), once every three months (Q3M), once every four months (Q4M), once every five months (Q5M), once every six months (Q6M), or at a less frequent frequency. In some embodiments, one or more multispecific antigen-binding molecules, polynucleotides, vectors, LNPs, and / or pharmaceutical compositions are administered intravenously or subcutaneously for two, three, four, or five or more doses at intervals of every other week (i.e., once every week or once every two weeks, or Q2W) to every three weeks (i.e., once every three weeks or Q3W). In some embodiments, the method involves one or more multispecific antigen-binding molecules having a serum half-life in humans of at least three days, e.g., at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least fifteen, or at least sixteen days. In some embodiments, the subject or mammal is human.In some embodiments, the subject is free from symptoms of HIV or AIDS for at least 6 months, at least 1 year, at least 2 years, or at least 3 years in the absence of antiretroviral therapy (ART). In some embodiments, the subject has a viral load of less than 500 copies / mL of blood for at least 6 months, at least 1 year, at least 2 years, or at least 3 years in the absence of antiretroviral therapy (ART), for example, less than 400, less than 300, less than 200, less than 100, or less than 50 copies / mL.

[0027] In related embodiments, methods are provided for treating or preventing HIV in human subjects who require such treatment. In some embodiments, the method includes (a) the following amino acid residues: N332glycan, D325, and T63, N332glycan, D325, and L179, N332glycan, D325, and T320, N332glycan, D325, and H330, N332glycan, D325, T63, and L179, N332glycan, D325, T63, and T320, N332glycan, D325, T63, and H330, N332glycan, D325, L179, and T320, N332glycan, D325, L179, and H330, N332glycan, D325, T320, and H330, N332glycan, D325, T63, T320, and H330, N332glycan, D325, T63, (b) Identifying a human subject infected with HIV expressing gp120 comprising L179 and T320, N332glycan, D325, T63, L179 and H330, N332glycan, D325, L179, T320 and H330, or N332glycan, D325, T63, L179, T320 and H330, wherein the position and residues are identified based on SEQ ID NO: 69; (b) administering to the subject an effective amount of the multispecific antigen-binding molecule or pharmaceutical composition described herein, wherein the second binding domain competes with or includes the VH and VL regions that bind to a third variable loop (V3) (e.g., a high-mannose patch) comprising N332 oligomannose glycan. In some embodiments, the method involves identifying a subject infected with HIV or an HIV population that expresses gp120 containing the following amino acid residues: N332glycan, D325, and T63, N332glycan, D325, and L179, N332glycan, D325, and T320, or N332glycan, D325, and H330.In some embodiments, the method involves identifying a subject infected with HIV or an HIV population that expresses gp120 containing the following amino acid residues: N332glycan, D325, T63, and L179; N332glycan, D325, T63, and T320; N332glycan, D325, T63, and H330; N332glycan, D325, L179, and T320; N332glycan, D325, L179, and H330; or N332glycan, D325, T320, and H330. In some embodiments, the method involves identifying a subject infected with HIV or an HIV population that expresses gp120 containing the following amino acid residues: N332glycan, D325, L179, T320, and H330; N332glycan, D325, T63, T320, and H330; N332glycan, D325, T63, L179, and T320; N332glycan, D325, T63, L179, and H330. In some embodiments, the method involves identifying a subject infected with HIV or an HIV population that expresses gp120 containing the following amino acid residues: N332glycan, D325, T63, and H330; N332glycan, D325, T320, and H330; N332glycan, D325, L179, T320, and H330; or N332glycan, D325, T63, L179, T320, and H330.In some embodiments, the second antigen-binding domain is 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-9721, GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-125, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, PGT-136, PGT-137, P Competing with or containing the VH and VL regions derived from antibodies selected from the group consisting of GT-138, PGT-139, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG42, 354BG33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03. In some embodiments, the second antigen-binding domain competes with or includes VH and VL regions derived from an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-9721, GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134. In some embodiments, the method involves performing the treatment or prophylaxis of HIV on a human subject in need of treatment or prophylaxis, the method comprising: (a) identifying an HIV-infected human subject expressing gp120 comprising the following amino acid residues: (i) I201 and F353, (ii) I201, I108 and F353, (iii) I201, I108, A281 and F353, (iv) I201, E102, I108, A281 and F353, (v) I201, E102, I108, A281, Y318 and F353, wherein the position and residue are identified based on SEQ ID NO: 73; and (b) administering to the subject an effective amount of a multispecific antigen-binding molecule or pharmaceutical composition according to any one of claims 123 to 154, wherein the second binding domain is gp120 The administration of a substance that competes with or contains the VH and VL regions that bind to the CD4 binding site (CD4bs).In some embodiments, the second antigen-binding domain competes with or includes VH and VL regions derived from antibodies selected from the group consisting of 3BNC117, GS-9723, GS-5423, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, VRC06b01, VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25. In some embodiments, the second primordial binding domain competes with or includes VH and VL regions derived from an antibody selected from the group consisting of 3BNC117, GS-9723, GS-5423, 3BNC60, VRC01, VRC07, and VRC07-523. In some embodiments, the method further comprises administering a second agent for treating HIV infection to a subject. In some embodiments, the subject is not receiving antiretroviral therapy (ART), or ART is discontinued before administration of one or more multispecific antigen-binding molecules. In some embodiments, ART is discontinued after one or more administrations of one or more multispecific antigen-binding molecules. In some embodiments, the method further comprises administering one or more antiretroviral therapy (ART) agents to a subject. In some embodiments, the method further comprises administering at least one of a TLR agonist and an IL-15 receptor agonist to a subject. In some embodiments, the method comprises administering a multispecific antigen-binding molecule having a first antigen-binding domain that binds to CD3, and a second antigen-binding domain that binds to the gp120 epitope or region of the CD4 binding site (CD4bs) and includes one or more extracellular (EC) domains of CD4, and optionally an IL-15 receptor agonist.In some embodiments, one or more EC domains of CD4 include a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the sequence shown in SEQ ID NOs. 746-749, or the amino acid sequence of SEQ ID NOs. 746-749 (e.g., SEQ ID NO. 746). In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 11, 8, 4, 9, and 10, or SEQ ID NOs: 1, 12, 8, 4, 9, and 10, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746), or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Chothia): SEQ ID NOs: 17, 18, 23, 20, 24, and 25, respectively, and the second antigen-binding domain is a CD4 selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746). The CD4 contains an EC domain, or one or more EC domains of CD4 containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10, respectively, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746 to 749 (e.g., SEQ ID NO. 746), or one or more CD4 EC domains comprising amino acid sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 42, 40, 37, 41, and 25, or SEQ ID NOs: 34, 43, 40, 37, 41, and 25, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746), or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH and a first VL, each containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequences: SEQ ID NOs: 49 and 55, SEQ ID NOs: 50 and 55, SEQ ID NOs: 50 and 56, SEQ ID NOs: 51 and 55, or SEQ ID NOs: 51 and 56, and the second antigen-binding domain comprises a CD4 selected from the group consisting of SEQ ID NOs: 746 to 749 (e.g., SEQ ID NO: 746). The TLR agonist comprises one or more EC domains of CD4, which include an EC domain or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the TLR agonist is a TLR2 agonist, a TLR3 agonist, a TLR7 agonist, a TLR8 agonist, or a TLR9 agonist. In some embodiments, the TLR7 agonist is selected from the group consisting of besatrimod, imiquimod, and reximod. In some embodiments, the method involves administering one or more multispecific antigen-binding molecules, optionally together with a TLR agonist, multiple times at predetermined intervals. In some embodiments, the subject is free from symptoms of HIV or AIDS for at least 6 months, at least 1 year, at least 2 years, or at least 3 years in the absence of antiretroviral therapy (ART). In some embodiments, the subject has a viral load of less than 500 copies / mL of blood for at least 6 months, at least 1 year, at least 2 years, or at least 3 years in the absence of antiretroviral therapy (ART), for example, less than 400, less than 300, less than 200, less than 100, or less than 50 copies / mL.

[0028] Further embodiments provide the use of a multispecific (e.g., bispecific) antigen-binding molecule or antigen-binding fragment thereof, or a pharmaceutical composition described herein, in a method of performing at least one of the treatment, prevention, and inhibition of HIV in a human subject requiring such treatment, prevention, and inhibition. Further embodiments provide a multispecific (e.g., bispecific) antigen-binding molecule or antigen-binding fragment thereof, or a pharmaceutical composition described herein, for use in a method of performing at least one of the treatment, prevention, and inhibition of HIV in a human subject requiring such treatment, prevention, and inhibition. In some embodiments, the use further comprises administering a second agent for the treatment of HIV infection to a subject. In some embodiments, the use further comprises administering at least one of a TLR agonist and an IL-15 receptor agonist to a subject. In some embodiments, the use involves administering a multispecific antigen-binding molecule having a first antigen-binding domain that binds to CD3 and a second antigen-binding domain that binds to the gp120 epitope or region of the CD4 binding site (CD4bs) and includes one or more extracellular (EC) domains of CD4, and optionally an IL-15 receptor agonist. In some embodiments, one or more EC domains of CD4 include a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the sequence shown in SEQ ID NOs. 746-749, or the amino acid sequence of SEQ ID NOs. 746-749 (e.g., SEQ ID NO. 746).In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 11, 8, 4, 9, and 10, or SEQ ID NOs: 1, 12, 8, 4, 9, and 10, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746), or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Chothia): SEQ ID NOs. 17, 18, 23, 20, 24, and 25, respectively, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746 to 749 (e.g., SEQ ID NO. 746), or one or more CD4 EC domains comprising amino acid sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10, respectively, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746 to 749 (e.g., SEQ ID NO. 746), or one or more CD4 EC domains comprising amino acid sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 42, 40, 37, 41, and 25, or SEQ ID NOs: 34, 43, 40, 37, 41, and 25, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746-749 (e.g., SEQ ID NO: 746), or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.In some embodiments, the first antigen-binding domain comprises a first VH and a first VL, each containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequences: SEQ ID NOs: 49 and 55, SEQ ID NOs: 50 and 55, SEQ ID NOs: 50 and 56, SEQ ID NOs: 51 and 55, or SEQ ID NOs: 51 and 56, and the second antigen-binding domain comprises a CD4 selected from the group consisting of SEQ ID NOs: 746 to 749 (e.g., SEQ ID NO: 746). The TLR agonist comprises one or more EC domains of CD4, which include an EC domain or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. In some embodiments, the TLR agonist is a TLR2 agonist, a TLR3 agonist, a TLR7 agonist, a TLR8 agonist, or a TLR9 agonist. In some embodiments, the TLR7 agonist is selected from the group consisting of besatrimod, imiquimod, and reximod. In some embodiments, use involves administering a first multispecific antigen-binding molecule and a second or additional antigen-binding molecule, the first multispecific antigen-binding molecule and the second or additional antigen-binding molecule binding to different first and second epitopes or regions of gp120 selected from the group consisting of (i) a third variable loop (V3) containing N332 oligomannose glycan (e.g., a high-mannose patch), (ii) a second variable loop (V2) (e.g., an Env trimer vertex), (iii) a CD4 binding site (CD4bs), (iv) a gp120 / gp41 interface, or (v) a silent surface of gp120. In some embodiments, the first multispecific antigen-binding molecule binds to a third variable loop (V3) containing N332 oligomannose glycan (e.g., a high-mannose patch), and the second antigen-binding molecule binds to a CD4 binding site (CD4bs).In some embodiments, the first multispecific antigen-binding molecule is 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-125, PGT-126, PGT-128, PGT-130, PGT-133, PG T-134, PGT-135, PGT-136, PGT-137, PGT-138, PGT-139, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG4 2, 354BG33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21 The second antigen-binding molecule competes with or contains the VH and VL regions of an antibody selected from the group consisting of PCDN-33A, BF520.1, and VRC29.03, and the second antigen-binding molecule is b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, VRC06b01, VRC08, VRC0801, NIH45-46, 3BNC117, 3BNC6 Competing with or containing the VH and VL regions derived from antibodies selected from the group consisting of 0, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25. In some embodiments, the first multispecific antigen-binding molecule competes with or includes VH and VL regions derived from an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134, and the second antigen-binding molecule competes with or includes VH and VL regions derived from 3BNC117, GS-9723, VRC07, or VRC07-523.In some embodiments, the first multispecific antigen-binding molecule competes with or includes the VH and VL regions of an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134, and the second antigen-binding molecule includes the EC domain of CD4. In some embodiments, the first multispecific antigen-binding molecule binds to a CD4 binding site (CD4bs), and the second or additional antigen-binding molecule binds to a third variable loop (V3) (e.g., a high-mannose patch) containing N332 oligomannose glycan. In some embodiments, the first multispecific antigen-binding molecule is GS-9723, GS-5423, 3BNC117, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, VRC06b01 The second or additional antigen-binding molecule competes with or includes the VH and VL regions of antibodies selected from the group consisting of VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25, and the second or additional antigen-binding molecule is GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-1 25, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, PGT-136, PGT-137, PGT-1 38, PGT-139, 10-1074, 10-1074-J, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG42, 354BG Competing with or containing the VH and VL regions derived from antibodies selected from the group consisting of 33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03.In some embodiments, the first multispecific antigen-binding molecule is G. The second or additional antigen-binding molecule competes with or includes the VH and VL regions derived from antibodies selected from the group consisting of S-9723, GS-5423, 3BNC117, VRC07, and VRC07-523, and competes with or includes the VH and VL regions derived from 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134. In some embodiments, the first multispecific antigen-binding molecule competes with or includes the EC domain of CD4, and the second or additional antigen-binding molecule is GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-125, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, PGT-136, PGT-137, PG Competing with or containing the VH and VL regions derived from antibodies selected from the group consisting of T-138, PGT-139, 10-1074, 10-1074-J, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG42, 354BG33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03. In some embodiments, the first multispecific antigen-binding molecule competes with or includes the EC domain of CD4, and the second or additional antigen-binding molecule competes with or includes the VH and VL regions of an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134.In some embodiments, use further comprises administering a second or additional antigen-binding molecule that competes with or includes the VH and VL regions derived from antibodies selected from the group consisting of GS-9723, GS-5423, 3BNC117, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, VRC06b01, VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25. In some embodiments, use further comprises administering a second or additional antigen-binding molecule that competes with or includes the VH and VL regions of an antibody selected from the group consisting of GS-9723, GS-5423, 3BNC117, VRC07, and VRC07-523. In some embodiments, use involves co-administration of (i) a multispecific antigen-binding molecule comprising the EC domain of CD4 as described herein, (ii) an antibody that competes with or contains the VH and VL regions of an antibody selected from the group consisting of 10-1074, 10-1074-J, GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, and PGT-134, and (iii) an antibody that competes with or contains the VH and VL regions of an antibody selected from the group consisting of GS-9723, GS 5423, 3BNC117, VRC07, and VRC07-523. In some embodiments, use further involves administering to a human subject an additional antigen-binding molecule or its antigen-binding fragment that performs at least one of binding to HIV, inhibiting it, and neutralizing it, or a polynucleotide encoding an additional antigen-binding molecule or its antigen-binding fragment.In some embodiments, the human subject is infected with HIV expressing gp120 containing the following amino acid residues: N332 / D325, N332 / D325 / H330, N332 / D325 / H330 / T320, N332 / D325 / H330 / T63, N332 / D325 / H330 / T63 / T320, or N332 / D325 / H330 / T63 / T320 / L179.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which the present invention relates. Methods and materials similar to or equivalent to those described herein may be used in carrying out or testing the bispecific molecules described herein, but exemplary methods and materials are described below. All publications, patent applications, patents, and other references referenced herein are incorporated in their entirety by reference. In case of any conflict, the application containing the definitions shall prevail. Materials, methods, and examples are illustrative and not intended to limit the scope of the invention.

[0030] Other features and advantages of the present invention will become apparent from the following embodiments and claims for carrying out the invention. In embodiments of the present invention, for example, the following items are provided. (Item 1) A multispecific antigen-binding molecule that binds to human CD3 and HIV antigen, wherein the antigen-binding molecule is (a) A first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), which binds to CD3, (i) The first VH complementarity Determining Region (CDR) 1, which contains the amino acid sequence of TYAMN (SEQ ID NO: 1) (ii) A first VH-CDR2 comprising the amino acid sequence RIRSKYNNYATYYAX1SVKX2 (wherein X1 is A or D and X2 is G or S) (Sequence ID 2), (iii) A first VH-CDR3 comprising the amino acid sequence HGNFGX3SYVSWFAY (wherein X3 is H or N) (SEQ ID NO: 3), (iv) The first VL-CDR1 containing the amino acid sequence of GSSTGAVTTGHYAN (SEQ ID NO: 4), (v) The first VL-CDR2 containing the amino acid sequence of GTX4X5RAP (wherein X4X5 is SN or NK) (SEQ ID NO: 5), and (vi) comprising a first VL-CDR3 having the amino acid sequence ALWYSNX6WV (wherein X6 is L or R) (SEQ ID NO: 6), wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VH-CDR3 have a first antigen-binding domain according to Kabat, (b) A multispecific antigen-binding molecule comprising a second antigen-binding domain that binds to the HIV antigen. (Item 2) A multispecific antigen-binding molecule that binds to human CD3 and the second antigen, wherein the antigen-binding molecule is (a) A first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), which binds to CD3, (i) The first VH complementarity Determining Region (CDR) 1, which contains the amino acid sequence of TYAMN (SEQ ID NO: 1) (ii) A first VH-CDR2 comprising the amino acid sequence RIRSKYNNYATYYAX1SVKX2 (wherein X1 is A or D and X2 is G or S) (Sequence ID 2), (iii) A first VH-CDR3 comprising the amino acid sequence HGNFGX3SYVSWFAY (wherein X3 is H or N) (SEQ ID NO: 3), (iv) The first VL-CDR1 containing the amino acid sequence of GSSTGAVTTGHYAN (SEQ ID NO: 4), (v) The first VL-CDR2 containing the amino acid sequence of GTX4X5RAP (wherein X4X5 is SN or NK) (SEQ ID NO: 5), and (vi) comprising a first VL-CDR3 having the amino acid sequence ALWYSNX6WV (wherein X6 is L or R) (SEQ ID NO: 6), wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VH-CDR3 have a first antigen-binding domain according to Kabat, (b) A multispecific antigen-binding molecule comprising a second antigen-binding domain that binds to a second antigen. (Item 3) (i) The first VH complementarity-determining region (CDR) 1 contains the amino acid sequence of TYAMN (SEQ ID NO: 1), (ii) The first VH-CDR2 contains the amino acid RIRSKYNNYATYYADSVKX2 (where X2 is G or S) (Sequence ID 7), (iii) The first VH-CDR3 contains the amino acid sequence HGNFGHSYVSWFAY (SEQ ID NO: 8), (iv) The first VL-CDR1 contains the amino acid sequence GSSTGAVTTGHYAN (SEQ ID NO: 4), (v) The first VL-CDR2 contains the amino acid sequence of GTSNRAP (SEQ ID NO: 9), (vi) The multispecific antigen-binding molecule described in item 1 or 2, wherein the first VL-CDR3 comprises the amino acid sequence of ALWYSNRWV (SEQ ID NO: 10). (Item 4) The first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each have the following amino acid sequence: (i) Sequence numbers 1, 11, 8, 4, 5, and 10, (ii) Sequence IDs 1, 11, 8, 4, 9, and 10, (iii) Sequence IDs 1, 12, 8, 4, 9, and 10, (iv) Sequence IDs 1, 13, 8, 4, 14, and 15, (v) Sequence IDs 1, 13, 16, 4, 14, and 15, or (vi) A multispecific antigen-binding molecule as described in any one of items 1 to 3, including SEQ ID NOs: 1, 11, 8, 4, 14, and 10. (Item 5) The first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each have the following amino acid sequence: (i) Sequence IDs 1, 11, 8, 4, 9, and 10, or (ii) A multispecific antigen-binding molecule as described in any one of items 1 to 4, including SEQ ID NOs: 1, 12, 8, 4, 9, and 10. (Item 6) A multispecific antigen-binding molecule according to any one of items 1 to 5, wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each contain the following amino acid sequences: SEQ ID NOs: 1, 11, 8, 4, 9, and 10. (Item 7) A multispecific antigen-binding molecule according to any one of items 1 to 5, wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each contain the following amino acid sequences: SEQ ID NOs: 1, 12, 8, 4, 9, and 10. (Item 8) A multispecific antigen-binding molecule that binds to human CD3 and HIV antigen, wherein the antigen-binding molecule is (a) A first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), which binds to CD3, (i) The first VH-CDR1 containing the amino acid sequence of GFTFNTY (SEQ ID NO: 17), (ii) The first VH-CDR2 containing the amino acid sequence of SKYNNY (SEQ ID NO: 18), (iii) A first VH-CDR3 comprising the amino acid sequence GNFGX3SYVSWFA (wherein X3 is H or N) (SEQ ID NO: 19), (iv) The first VL-CDR1 containing the amino acid sequence of SSTGAVTTGHY (SEQ ID NO: 20), (v) The first VL-CDR2 containing the amino acid sequence of GTX4 (where X4 is N or S) (SEQ ID NO: 21), and (vi) comprising a first VL-CDR3 having the amino acid sequence WYSNX6W (wherein X6 is L or R) (SEQ ID NO: 22), wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VH-CDR3 have a first antigen-binding domain that conforms to Chothia, (b) A multispecific antigen-binding molecule comprising a second antigen-binding domain that binds to the HIV antigen. (Item 9) A multispecific antigen-binding molecule that binds to human CD3 and the second antigen, wherein the antigen-binding molecule is (a) A first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), which binds to CD3, (i) The first VH-CDR1 containing the amino acid sequence of GFTFNTY (SEQ ID NO: 17), (ii) The first VH-CDR2 containing the amino acid sequence of SKYNNY (SEQ ID NO: 18), (iii) A first VH-CDR3 comprising the amino acid sequence GNFGX3SYVSWFA (wherein X3 is H or N) (SEQ ID NO: 19), (iv) The first VL-CDR1 containing the amino acid sequence of SSTGAVTTGHY (SEQ ID NO: 20), (v) The first VL-CDR2 containing the amino acid of GTX4 (where X4 is N or S in the sequence) (SEQ ID NO: 21), and (vi) comprising a first VL-CDR3 having the amino acid sequence WYSNX6W (wherein X6 is L or R) (SEQ ID NO: 22), wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VH-CDR3 have a first antigen-binding domain that conforms to Chothia, (b) A multispecific antigen-binding molecule comprising a second antigen-binding domain that binds to a second antigen. (Item 10) The first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each have the following amino acid sequence: (i) Sequence IDs 17, 18, 23, 20, 21, and 25, (ii) Sequence IDs 17, 18, 23, 20, 24, and 25, (iii) Sequence IDs 17, 18, 23, 20, 26, and 27, (iv) Sequence IDs 17, 18, 75, 20, 26, and 27, or (v) A multispecific antigen-binding molecule as described in item 8 or 9, including sequence numbers 17, 18, 23, 20, 26, and 25. (Item 11) A multispecific antigen-binding molecule according to any one of items 8 to 10, wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each contain the following amino acid sequences: SEQ ID NOs: 17, 18, 23, 20, 24, and 25. (Item 12) A multispecific antigen-binding molecule that binds to human CD3 and HIV antigen, wherein the antigen-binding molecule is (a) A first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), which binds to CD3, (i) The first VH-CDR1 containing the amino acid sequence of GFTFNTYA (SEQ ID NO: 28), (ii) The first VH-CDR2 containing the amino acid sequence of IRSKYNNYAT (SEQ ID NO: 29), (iii) A first VH-CDR3 comprising the amino acid sequence VRHGNFGX3SYVSWFAY (wherein X3 is H or N) (SEQ ID NO: 30), (iv) The first VL-CDR1 containing the amino acid sequence of TGAVTTGHY (SEQ ID NO: 31), (v) The first VL-CDR2 containing the amino acid sequence of GTX4 (where X4 is N or S) (SEQ ID NO: 21), and (vi) comprising a first VL-CDR3 having the amino acid sequence ALWYSNX6WV (wherein X6 is L or R) (SEQ ID NO: 6), wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VH-CDR3 have a first antigen-binding domain according to IMGT, (b) A multispecific antigen-binding molecule comprising a second antigen-binding domain that binds to the HIV antigen. (Item 13) A multispecific antigen-binding molecule that binds to human CD3 and the second antigen, wherein the antigen-binding molecule is (a) A first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), which binds to CD3, (i) The first VH-CDR1 containing the amino acid sequence of GFTFNTYA (SEQ ID NO: 28), (ii) The first VH-CDR2 containing the amino acid sequence of IRSKYNNYAT (SEQ ID NO: 29), (iii) A first VH-CDR3 comprising the amino acid sequence VRHGNFGX3SYVSWFAY (wherein X3 is H or N) (SEQ ID NO: 30), (iv) The first VL-CDR1 containing the amino acid sequence of TGAVTTGHY (SEQ ID NO: 31), (v) The first VL-CDR2 containing the amino acid sequence of GTX4 (where X4 is N or S) (SEQ ID NO: 21), and (vi) comprising a first VL-CDR3 having the amino acid sequence ALWYSNX6WV (wherein X6 is L or R) (SEQ ID NO: 6), wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VH-CDR3 have a first antigen-binding domain according to IMGT, (b) A multispecific antigen-binding molecule comprising a second antigen-binding domain that binds to a second antigen. (Item 14) The first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each have the following amino acid sequence: (i) Sequence IDs 28, 29, 32, 31, 21, and 10, (ii) Sequence IDs 28, 29, 32, 31, 24, and 10, (iii) Sequence IDs 28, 29, 32, 31, 26, and 15, (iv) Sequence IDs 28, 29, 33, 31, 26, and 15, or (v) A multispecific antigen-binding molecule as described in item 12 or 13, including sequence numbers 28, 29, 32, 31, 26, and 10. (Item 15) A multispecific antigen-binding molecule according to any one of items 12 to 14, wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each contain the following amino acid sequences: SEQ ID NOs: 28, 29, 32, 31, 24, and 10. (Item 16) A multispecific antigen-binding molecule that binds to human CD3 and HIV antigen, wherein the antigen-binding molecule is (a) A first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), which binds to CD3, (i) The first VH-CDR1 containing the amino acid sequence ASGFTFNTYA (SEQ ID NO: 34), (ii) A first VH-CDR2 comprising the amino acid sequence IRSKYNNYATYYAX1SVKX2R (wherein X1 is A or D, and X2 is G or S) (Sequence ID 35), (iii) A first VH-CDR3 comprising the amino acid sequence HGNFGX3SYVSWFA (where X3 is H or N) (SEQ ID NO: 36), (iv) The first VL-CDR1 containing the amino acid sequence of SSTGAVTTGHY (SEQ ID NO: 37), (v) The first VL-CDR2 containing the amino acid sequence of (v) GTX4NRAPX7VPAR (wherein X4 is N or S and X7 is G or W) (SEQ ID NO: 38), and (vi) comprising a first VL-CDR3 having the amino acid sequence WYSNX6W (wherein X6 is L or R) (SEQ ID NO: 22), wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VH-CDR3 each have a first antigen-binding domain according to Honegger, (b) A multispecific antigen-binding molecule comprising a second antigen-binding domain that binds to the HIV antigen. (Item 17) A multispecific antigen-binding molecule that binds to human CD3 and the second antigen, wherein the antigen-binding molecule is (a) A first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), which binds to CD3, (i) The first VH-CDR1 containing the amino acid sequence ASGFTFNTYA (SEQ ID NO: 34), (ii) A first VH-CDR2 comprising the amino acid sequence IRSKYNNYATYYAX1SVKX2R (wherein X1 is A or D, and X2 is G or S) (Sequence ID 35), (iii) A first VH-CDR3 comprising the amino acid sequence HGNFGX3SYVSWFA (where X3 is H or N) (SEQ ID NO: 36), (iv) The first VL-CDR1 containing the amino acid sequence of SSTGAVTTGHY (SEQ ID NO: 37), (v) The first VL-CDR2 containing the amino acid sequence of (v) GTX4NRAPX7VPAR (wherein X4 is N or S and X7 is G or W) (SEQ ID NO: 38), and (vi) comprising a first VL-CDR3 having the amino acid sequence WYSNX6W (wherein X6 is L or R) (SEQ ID NO: 22), wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VH-CDR3 each have a first antigen-binding domain according to Honegger, (b) A multispecific antigen-binding molecule comprising a second antigen-binding domain that binds to a second antigen. (Item 18) (i) The first VH-CDR1 contains the amino acid sequence ASGFTFNTYA (SEQ ID NO: 34), (ii) The first VH-CDR2 comprises the amino acid sequence IRSKYNNYATYYADSVKX2R (where X2 is G or S) (Sequence ID 39), (iii) The first VH-CDR3 contains the amino acid sequence HGNFGHSYVSWFA (SEQ ID NO: 40), (iv) The first VL-CDR1 comprises the amino acid sequence SSTGAVTTGHY (SEQ ID NO: 37), (v) The first VL-CDR2 contains the amino acid sequence of GTSNRAPGVPAR (SEQ ID NO: 41), (vi) The first VL-CDR3 is a multispecific antigen-binding molecule as described in item 16 or 17, comprising the amino acid sequence of WYSNRW (SEQ ID NO: 25). (Item 19) The first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each have the following amino acid sequence: (i) Sequence IDs 34, 39, 40, 37, 41, and 25, (ii) Sequence IDs 34, 42, 40, 37, 41, and 25, (iii) Sequence IDs 34, 43, 40, 37, 41, and 25, (iv) Sequence IDs 34, 44, 40, 37, 45, and 27, (v) Sequence IDs 34, 44, 46, 37, 45, and 27, or (vi) A multispecific antigen-binding molecule as described in any one of items 16 to 18, including SEQ ID NOs: 34, 42, 40, 37, 47, and 25. (Item 20) The first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each have the following amino acid sequence: (i) Sequence IDs 34, 42, 40, 37, 41, and 25, or (ii) A multispecific antigen-binding molecule as described in any one of items 16 to 19, including SEQ ID NOs: 34, 43, 40, 37, 41, and 25. (Item 21) A multispecific antigen-binding molecule according to any one of items 16 to 20, wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each contain the following amino acid sequences: SEQ ID NOs: 34, 42, 40, 37, 41, and 25. (Item 22) A multispecific antigen-binding molecule according to any one of items 16 to 20, wherein the first VH-CDR1, the first VH-CDR2, the first VH-CDR3, the first VL-CDR1, the first VL-CDR2, and the first VL-CDR3 each contain the following amino acid sequences: SEQ ID NOs: 34, 43, 40, 37, 41, and 25. (Item 23) The following amino acid substitutions (numbering follows Kabat): (i) The 81st position of the first VH is Q or E, (ii) The 83rd position of the first VH is K or R, (iii) The 89th position of the first VH is M or V, (iv) The 100th position of the first VH is H. (v) The 57th position of the first VL is G or W, and / or (vi) A multispecific antigen-binding molecule according to any one of items 1 to 22, comprising one or more of the following: the 75th position of the first VL is I or L. (Item 24) The multispecific antigen-binding molecule described in item 23, wherein the 81st position of the first VH (numbering follows Kabat) is E. (Item 25) The multispecific antigen-binding molecule described in item 23, wherein the 81st position of the first VH (numbering follows Kabat) is Q. (Item 26) The following amino acid substitutions (numbering follows Kabat): (i) The 81st position of the first VH is Q or E, (ii) The 83rd position of the first VH is R. (iii) The 89th position of the first VH is V. (iv) The 100th position of the first VH is H. (v) The 57th position of the first VL is G, and / or (vi) A multispecific antigen-binding molecule as described in item 23, comprising one or more of the following, wherein the 75th position of the first VL is I. (Item 27) A multispecific antigen-binding molecule according to any one of items 1 to 25, wherein the first VH contains an amino acid sequence selected from the group consisting of SEQ ID NOs. 48 to 53, or contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs. 48 to 53. (Item 28) A multispecific antigen-binding molecule according to any one of items 1 to 27, wherein the first VH comprises an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 50. (Item 29) A multispecific antigen-binding molecule according to any one of items 1 to 28, wherein the first VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 50. (Item 30) A multispecific antigen-binding molecule according to any one of items 1 to 29, wherein the first VH comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 50. (Item 31) The first VH is a multispecific antigen-binding molecule according to any one of items 1 to 30, comprising the amino acid sequence of SEQ ID NO: 50. (Item 32) A multispecific antigen-binding molecule according to any one of items 1 to 27, wherein the first VH comprises an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 51. (Item 33) A multispecific antigen-binding molecule according to any one of items 1 to 32, wherein the first VH comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 51. (Item 34) A multispecific antigen-binding molecule according to any one of items 1 to 33, wherein the first VH comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 51. (Item 35) The first VH is a multispecific antigen-binding molecule according to any one of items 1 to 34, comprising the amino acid sequence of SEQ ID NO: 51. (Item 36) A multispecific antigen-binding molecule according to any one of items 1 to 35, wherein the first VL contains an amino acid sequence selected from the group consisting of SEQ ID NOs. 54 to 58, or contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs. 54 to 58. (Item 37) A multispecific antigen-binding molecule according to any one of items 1 to 36, wherein the first VL contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 56. (Item 38) A multispecific antigen-binding molecule according to any one of items 1 to 37, wherein the first VL contains an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 56. (Item 39) A multispecific antigen-binding molecule according to any one of items 1 to 38, wherein the first VL contains an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 56. (Item 40) The first VL is a multispecific antigen-binding molecule according to any one of items 1 to 39, comprising the amino acid sequence of SEQ ID NO: 56. (Item 41) A multispecific antigen-binding molecule according to any one of items 1 to 40, wherein the first VH includes an amino acid sequence selected from the group consisting of SEQ ID NOs. 48 to 53, or includes an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs. 48 to 53, and the first VL includes an amino acid sequence selected from the group consisting of SEQ ID NOs. 54 to 58, or includes an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs. (Item 42) The first VH and the first VL each contain the amino acid sequence shown below, or each contains the amino acid sequence shown below: i. Sequence IDs 48 and 54, ii. Sequence IDs 49 and 55, iii. Sequence IDs 50 and 55, iv. Sequence IDs 50 and 56, v. Sequence IDs 51 and 55, vi. Sequence IDs 51 and 56, vii. Sequence IDs 52 and 56, viii. Sequence IDs 53 and 57, or ix. A multispecific antigen-binding molecule according to any one of items 1 to 41, comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NOs. 50 and 58. (Item 43) The first VH and the first VL each contain the amino acid sequence shown below, or each contains the amino acid sequence shown below: i. Sequence IDs 49 and 55, ii. Sequence IDs 50 and 55, iii. Sequence IDs 50 and 56, iv. Sequence IDs 51 and 55, or A multispecific antigen-binding molecule according to any one of items 1 to 42, comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NOs. 51 and 56. (Item 44) A multispecific antigen-binding molecule according to any one of items 1 to 43, wherein the first VH and the first VL each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequences shown below: SEQ ID NOs: 50 and 56. (Item 45) A multispecific antigen-binding molecule according to any one of items 1 to 44, wherein the first VH and the first VL each contain an amino acid sequence that is at least 95% identical to the amino acid sequences shown below: SEQ ID NOs: 50 and 56. (Item 46) A multispecific antigen-binding molecule according to any one of items 1 to 45, wherein the first VH and the first VL each contain an amino acid sequence that is at least 99% identical to the amino acid sequences shown below: SEQ ID NOs: 50 and 56. (Item 47) A multispecific antigen-binding molecule according to any one of items 1 to 46, wherein the first VH and the first VL each contain the amino acid sequences shown below: SEQ ID NOs: 50 and 56. (Item 48) A multispecific antigen-binding molecule according to any one of items 1 to 43, wherein the first VH and the first VL each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequences shown below: SEQ ID NOs: 51 and 56. (Item 49) A multispecific antigen-binding molecule according to any one of items 1 to 48, wherein the first VH and the first VL each contain an amino acid sequence that is at least 95% identical to the amino acid sequences shown below: SEQ ID NOs: 51 and 56. (Item 50) A multispecific antigen-binding molecule according to any one of items 1 to 49, wherein the first VH and the first VL each contain an amino acid sequence that is at least 99% identical to the amino acid sequences shown below: SEQ ID NOs: 51 and 56. (Item 51) A multispecific antigen-binding molecule according to any one of items 1 to 50, wherein the first VH and the first VL each contain the amino acid sequences shown below: SEQ ID NOs: 51 and 56. (Item 52) A multispecific antigen-binding molecule as described in any one of items 23 to 51, wherein the amino acid residue at position 100 of the first VH (numbering follows Kabat) is H. (Item 53) A multispecific antigen-binding molecule according to any one of items 1 to 52, wherein at least one of the first antigen-binding domain and the second antigen-binding domain independently comprises Fab, F(ab)2, Fv, scFv, sc(Fv)2, or a diabody. (Item 54) i. The first antigen-binding domain contains scFv, and the second antigen-binding domain contains Fab, ii. The first antigen-binding domain contains Fab, and the second antigen-binding domain contains scFv, iii. The first antigen-binding domain contains Fab, and the second antigen-binding domain contains Fab, or iv. A multispecific antigen-binding molecule according to any one of items 1 to 53, wherein the first antigen-binding domain comprises an scFv and the second antigen-binding domain comprises an scFv. (Item 55) A multispecific antigen-binding molecule according to any one of items 1 to 54, wherein the first antigen-binding domain comprises scFv and the second antigen-binding domain comprises Fab. (Item 56) i. The first antigen-binding domain includes Fab, and the second antigen-binding domain includes the extracellular domain of CD4, or ii. A multispecific antigen-binding molecule according to any one of items 1 to 53, wherein the first antigen-binding domain comprises scFv and the second antigen-binding domain comprises the extracellular domain of CD4. (Item 57) A multispecific antigen-binding molecule as described in any one of items 1 to 53, wherein the first antigen-binding domain comprises Fab and the second antigen-binding domain comprises the extracellular domain of CD4. (Item 58) The following amino acid substitutions (numbering follows Kabat): i. Cysteine ​​(C) at position 44 of the scFv variable weight domain, and ii. A multispecific antigen-binding molecule according to item 56 or 57, comprising cysteine ​​(C) at position 100 of the scFv variable light domain. (Item 59) A multispecific antigen-binding molecule according to any one of items 1 to 56 and 58, wherein the first antigen-binding domain is an scFv containing VH and VL, and the scFv contains an amino acid sequence selected from SEQ ID NOs. 59 to 66, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence selected from SEQ ID NOs. 59 to 66. (Item 60) A multispecific antigen-binding molecule according to any one of items 1 to 56 and 58 or 59, wherein the first antigen-binding domain is an scFv comprising VH and VL, and the scFv comprises an amino acid sequence selected from SEQ ID NOs. 59 to 63, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to an amino acid sequence selected from SEQ ID NOs. 59 to 63. (Item 61) A multispecific antigen-binding molecule according to any one of items 1 to 56 and 58 or 59, wherein the first antigen-binding domain is an scFv comprising VH and VL, and the scFv comprises an amino acid sequence selected from SEQ ID NO: 62 or 63, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence selected from SEQ ID NO: 62 or 63. (Item 62) The multispecific antigen-binding molecule according to item 61, wherein the first antigen-binding domain is an scFv comprising VH and VL, and the scFv comprises an amino acid sequence selected from SEQ ID NO: 62, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 62. (Item 63) The multispecific antigen-binding molecule according to item 61, wherein the first antigen-binding domain is an scFv comprising VH and VL, and the scFv comprises an amino acid sequence selected from SEQ ID NO: 63, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 63 or 63. (Item 64) A multispecific antigen-binding molecule according to any one of items 1-54 and 58-61, wherein the second antigen-binding domain binds to an HIV envelope protein selected from the group consisting of gp120 and gp41. (Item 65) A multispecific antigen-binding molecule according to any one of items 1 to 64, wherein the second antigen-binding domain competes with or includes the VH and VL variable domains of a broadly neutralizing antibody (bNAb) against HIV. (Item 66) The second antigen-binding domain described above is i. A third variable loop (V3) containing N332 oligomannose glycan (e.g., a high-mannose patch), ii. The second variable loop (V2) (e.g., the vertices of the Env trimer), iii.CD4 binding site (CD4bs), iv. GP120 / GP41 interface, or A multispecific antigen-binding molecule according to any one of items 1-54 and 58-65, which binds to an epitope or region of gp120 selected from the group consisting of the silent surface of v.gp120. (Item 67) The second antigen-binding domain binds to an epitope or region of gp120 within the third variable loop (V3) containing N332 oligomannose glycan (e.g., a high-mannose patch), and is used with GS-9722 (eripovimab), GS-2872, PGT-121, PGT-121.66, PGT-121.414, PGT-122, PGT-123, PGT-124, PGT-125, PGT-126, PGT-128, PGT-130, PGT-133, PGT-134, PGT-135, PGT-136, PGT-137, PGT-138, PGT- A multispecific antigen-binding molecule described in any one of items 1-54 and 58-66, which competes with or contains the VH and VL regions derived from an antibody selected from the group consisting of 139, 10-1074, 10-1074-J, VRC24, 2G12, BG18, 354BG8, 354BG18, 354BG42, 354BG33, 354BG129, 354BG188, 354BG411, 354BG426, DH270.1, DH270.6, PGDM12, VRC41.01, PGDM21, PCDN-33A, BF520.1, and VRC29.03. (Item 68) A multispecific antigen-binding molecule according to any one of items 1-54 and 58-66, wherein the second antigen-binding domain binds to an epitope or region of gp120 within the second variable loop (V2) (e.g., the apex of the Env trimer) and competes with, or includes, the VH and VL regions derived from an antibody selected from the group consisting of PG9, PG16, PGC14, PGG14, PGT-142, PGT-143, PGT-144, PGT-145, CH01, CH59, PGDM1400, CAP256, CAP256-VRC26.08, CAP256-VRC26.09, CAP256-VRC26.25, PCT64-24E, and VRC38.01. (Item 69) The second antigen-binding domain binds to the gp120 epitope or region within the CD4 binding site (CD4bs), and is associated with 3BNC117, GS-9723, GS-5423, 3BNC60, b12, F105, VRC01, VRC07, VRC07-523, VRC03, VRC06, and VRC06b01. A multispecific antigen-binding molecule described in any one of items 1-54 and 58-66, which competes with or contains the VH and VL regions derived from an antibody selected from the group consisting of VRC08, VRC0801, NIH45-46, PGV04 (also known as VRC-PG04); CH103, 44-VRC13.01, 1NC9, 12A12, N6, 1-18, N49-P7, NC-Cow1, IOMA, CH235 and CH235.12, N49P6, N49P7, N49P11, N49P9, and N60P25. (Item 70) A multispecific antigen-binding molecule according to any one of items 1 to 64 and 66, wherein the second antigen-binding domain binds to an epitope or region of gp120 within the CD4-binding site (CD4bs), and comprises one or more extracellular (EC) domains of CD4. (Item 71) One or more EC domains of the aforementioned CD4 are sequences shown below, or sequences selected from the group consisting of the following: (i)KKVVYGKKGDTVELTCTASQKKNIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRVDSRRSLWDQGNFPLIIKNLKPEDSDTYICEVEDQKEEVQLVVVG (Sequence ID 746), (ii) KKVVYGKKGDTVELTCTASQKKNIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRVDSRRSLWDQGNFPLIIKNLKPEDSDTYICEVEDQKEEVQLVVVGGGGSGKKVVYGKKGDTVELTCTASQKKNIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRVDSRRSLWDQGNFPLIIKNLKPEDSDTYICEVEDQKEEVQLVVVG (Sequence ID 747), (iii)KKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQLLVFG (Sequence ID 748), or (iv) A multispecific antigen-binding molecule as described in item 70, comprising a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to (sequence number 749). (Item 72) The multispecific antigen-binding molecule according to item 71, wherein the EC domain of the CD4 contains a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the sequence of sequence number 746. (Item 73) A multispecific antigen-binding molecule according to item 71 or 72, comprising a sequence in which the EC domain of CD4 is at least 95% identical to the sequence of sequence number 746. (Item 74) A multispecific antigen-binding molecule according to any one of items 71 to 73, comprising a sequence in which the EC domain of the CD4 is at least 99% identical to the sequence of sequence number 746. (Item 75) The multispecific antigen-binding molecule described in any one of items 71 to 74, wherein the EC domain of the CD4 contains the sequence of sequence number 746. (Item 76) A multispecific antigen-binding molecule according to any one of items 71 to 75, wherein the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 11, 8, 4, 9, and 10, or SEQ ID NOs: 1, 12, 8, 4, 9, and 10, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746 to 749, or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. (Item 77) The multispecific antigen-binding molecule described in item 76, wherein the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Kabat): SEQ ID NOs: 1, 12, 8, 4, 9, and 10, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746, or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. (Item 78) A multispecific antigen-binding molecule according to any one of items 71 to 75, wherein the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Chothia): SEQ ID NOs: 17, 18, 23, 20, 24, and 25, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746 to 749, or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. (Item 79) The multispecific antigen-binding molecule described in item 78, wherein the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Chothia): SEQ ID NOs. 17, 18, 23, 20, 24, and 25, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746, or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. (Item 80) A multispecific antigen-binding molecule according to any one of items 71 to 75, wherein the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746 to 749, or one or more CD4 EC domains comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. (Item 81) The multispecific antigen-binding molecule described in item 80, wherein the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to IMGT): SEQ ID NOs. 28, 29, 32, 31, 24, and 10, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs. 746, or one or more CD4 EC domains comprising an amino acid sequence identical thereto by at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%. (Item 82) The first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each containing the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 42, 40, 37, 41, and 25, or SEQ ID NOs: 34, 43, 40, 37, 41, and 25, and the second antigen-binding domain is a CD4 selected from the group consisting of SEQ ID NOs: 746-749. A multispecific antigen-binding molecule according to any one of items 71 to 75, comprising one or more EC domains of CD4, which include an EC domain or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. (Item 83) The multispecific antigen-binding molecule described in item 82, wherein the first antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3, each comprising the following amino acid sequences (according to Honegger): SEQ ID NOs: 34, 43, 40, 37, 41, and 25, and the second antigen-binding domain comprises a CD4 EC domain selected from the group consisting of SEQ ID NOs: 746, or one or more EC domains of CD4 comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. (Item 84) The first antigen-binding domain comprises a first VH and a first VL, each containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown in SEQ ID NOs. 49 and 55, SEQ ID NOs. 50 and 55, SEQ ID NOs. 50 and 56, or SEQ ID NOs. 51 and 56, respectively; the second antigen-binding domain comprises a first VH-CDR1, a first VH-CDR2, a first VH-CDR3, a first VL-CDR1, a first VL-CDR2, and a first VL-CDR3; and the second antigen-binding domain comprises a CD4 selected from the group consisting of SEQ ID NOs. 746 to 749. A multispecific antigen-binding molecule according to any one of items 71 to 75, comprising one or more EC domains of CD4, which include an EC domain or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto. (Item 85) A multispecific antigen-binding molecule according to any one of items 71 to 84, wherein the first antigen-binding domain comprises a first VH and a first VL, each comprising an amino acid sequence that includes the amino acid sequence shown in SEQ ID NOs. 51 and 56, respectively, or an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown therein, and the second antigen-binding domain comprises a CD4 EC domain that includes the CD4 EC domain of SEQ ID NOs. 746, or a single CD4 EC domain that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to it. (Item 86) The multispecific antigen-binding molecule according to item 85, wherein the first antigen-binding domain comprises a first VH and a first VL, each containing an amino acid sequence that is at least 95% identical to the amino acid sequences shown in SEQ ID NOs. 51 and 56, respectively, and the second antigen-binding domain comprises one EC domain of CD4 containing an amino acid sequence that is at least 95% identical to the CD4 EC domain of SEQ ID NO. 746. (Item 87) The multispecific antigen-binding molecule according to item 86, wherein the first antigen-binding domain comprises a first VH and a first VL, each containing an amino acid sequence that is at least 99% identical to the amino acid sequences shown in SEQ ID NOs. 51 and 56, respectively, and the second antigen-binding domain comprises one EC domain of CD4 containing an amino acid sequence that is at least 99% identical to the CD4 EC domain of SEQ ID NO. 746. (Item 88) The multispecific antigen-binding molecule according to item 87, wherein the first antigen-binding domain comprises a first VH and a first VL containing the amino acid sequences shown in SEQ ID NOs. 51 and 56, respectively, and the second antigen-binding domain comprises one EC domain of CD4 containing the amino acid sequence of SEQ ID NO. 746. (Item 89) A multispecific antigen-binding molecule according to any one of items 1-54 and 58-69, wherein the second antigen-binding domain binds to an epitope or region of gp120 at the gp120 / gp41 interface and competes with, or includes, VH and VL regions derived from an antibody selected from the group consisting of PGT-151, CAP248-2B, 35O22, 8ANC195, ACS202, VRC34, and VRC34.01. (Item 90) A multispecific antigen-binding molecule according to any one of items 1-54 and 58-69, wherein the second antigen-binding domain binds to an epitope or region of the gp120 silent surface and competes with, or includes, VH and VL regions derived from an antibody selected from VRC-PG05 and SF12. (Item 91) A multispecific antigen-binding molecule according to any one of items 1-54 and 58-69, wherein the second antigen-binding domain binds to the gp41 epitope or region of the membrane proximal region (MPER). (Item 92) The multispecific antigen-binding molecule described in item 91, wherein the second antigen-binding domain binds to an epitope or region of gp41 in the membrane proximal region (MPER) and competes with, or contains, VH and VL regions derived from an antibody selected from the group consisting of 10E8, 10E8v4, 10E8-5R-100cF, 4E10, DH511.11P, 2F5, 7b2, and LN01. (Item 93) A multispecific antigen-binding molecule according to any one of items 1-54 and 58-66, wherein the second antigen-binding domain binds to an epitope or region of the gp41 fusion peptide and competes with, or includes, VH and VL regions derived from an antibody selected from the group consisting of VRC34 and ACS202. (Item 94) The second antigen-binding domain comprises a second VH containing a second VH-CDR1, a second VH-CDR2, and a second VH-CDR3, and a second VL containing a second VL-CDR1, a second VL-CDR2, and a second VH-CDR3, each having the following amino acid sequence (according to Kabat): a) Sequence IDs 76, 77, 78, 79, 80, and 81, b) Sequence IDs 76, 82, 78, 79, 80, and 81, c) Sequence IDs 83, 84, 85, 86, 80, and 87, d) Sequence IDs 83, 88, 85, 86, 80, and 87, e) Sequence IDs 90, 91, 92, 93, 94, and 95, f) Sequence IDs 90, 91, 96, 93, 94, and 95, g) Sequence IDs 97, 98, 99, 100, 101, and 102, h) Sequence IDs 103, 104, 105, 106, 94, and 107, i) Sequence numbers 108, 109, 110, 111, 112, and 113, j) Sequence numbers 114, 115, 116, 117, 118, and 119, k) Sequence IDs 114, 120, 121, 122, 118, and 123, l) Sequence IDs 124, 125, 126, 127, 128, and 113, m) Sequence numbers 129, 115, 131, 127, 118, and 113, n) Sequence IDs 132, 133, 134, 135, 136, and 137, o) Sequence IDs 138, 139, 140, 141, 142, and 143, p) Sequence IDs 144, 145, 146, 147, 148, and 143, q) Sequence IDs 149, 150, 151, 152, 153, and 143, r) Sequence IDs 154, 155, 156, 157, 158, and 159, s) Sequence IDs 160, 161, 162, 163, 164, and 165, t) Sequence IDs 166, 161, 167, 163, 164, and 165, u) Sequence IDs 168, 169, 170, 171, 172, and 173, v) Sequence IDs 168, 174, 170, 171, 172, and 173, w) Sequence numbers 175, 176, 177, 171, 172, and 173, x) Sequence IDs 178, 179, 180, 181, 182, and 183, y) Sequence numbers 184, 185, 186, 187, 188, and 189, z) Sequence numbers 190, 191, 192, 193, 194, and 195, aa) Sequence IDs 196, 197, 198, 199, 200, and 201, bb) Sequence IDs 202, 203, 204, 205, 206, and 207, cc) Sequence IDs 208, 209, 210, 211, 212, and 213, dd) Sequence IDs 214, 215, 216, 217, 218, and 219, ee) Sequence IDs 214, 220, 216, 221, 218, and 219, ff) Sequence IDs 214, 220, 222, 221, 218, and 219, gg) Sequence IDs 223, 224, 225, 226, 227, and 228, hh) Sequence IDs 229, 230, 231, 232, 233, and 234, ii) Sequence IDs 902, 903, 904, 905, 906, and 907, jj) Sequence IDs 908, 909, 910, 911, 912, and 913, kk) Sequence IDs 914, 915, 916, 917, 918, and 919, or ll) A multispecific antigen-binding molecule as described in any one of items 1-54, 58-69, and 89-93, including sequence numbers 920, 921, 922, 923, 924, and 925. (Item 95) The second antigen-binding domain comprises a second VH containing a second VH-CDR1, a second VH-CDR2, and a second VH-CDR3, and a second VL containing a second VL-CDR1, a second VL-CDR2, and a second VH-CDR3, each having the following amino acid sequence (according to Chothia): a) Sequence IDs 235, 236, 237, 238, 239, and 240, b) Sequence IDs 241, 242, 243, 244, 239, and 245, c) Sequence IDs 246, 242, 247, 244, 239, and 245, d) Sequence IDs 248, 249, 250, 251, 239, and 252, e) Sequence IDs 248, 249, 253, 251, 239, and 252, f) Sequence IDs 254, 255, 256, 257, 258, and 259, g) Sequence IDs 260, 261, 262, 263, 239, and 264, h) Sequence IDs 265, 266, 267, 268, 269, and 270, i) Sequence IDs 271, 272, 273, 274, 275, and 270, j) Sequence IDs 271, 276, 277, 278, 275, and 279, k) Sequence IDs 280, 281, 282, 283, 284, and 270, l) Sequence IDs 285, 272, 286, 283, 275, and 270, m) Sequence IDs 287, 288, 289, 290, 291, and 292, n) Sequence IDs 293, 294, 295, 296, 297, and 298, o) Sequence IDs 299, 300, 301, 302, 303, and 298, p) Sequence IDs 304, 300, 305, 406, 307, and 298, q) Sequence numbers 308, 309, 310, 311, 312, and 313, r) Sequence IDs 314, 315, 316, 317, 318, and 165, s) Sequence IDs 320, 315, 321, 317, 318, and 165, t) Sequence IDs 322, 323, 324, 325, 326, and 327, u) Sequence IDs 322, 328, 324, 325, 326, and 327, v) Sequence IDs 329, 323, 330, 325, 326, and 327, w) Sequence numbers 331, 332, 333, 334, 335, and 336, x) Sequence numbers 337, 338, 339, 340, 341, and 342, y) Sequence numbers 343, 344, 345, 346, 341, and 347, z) Sequence numbers 348, 349, 350, 351, 352, and 353, aa) Sequence IDs 354, 355, 356, 357, 358, and 359, bb) Sequence numbers 360, 361, 362, 363, 364, and 365, cc) Sequence IDs 366, 367, 368, 369, 370, and 371, dd) Sequence numbers 366, 361, 368, 369, 370, and 371, ee) Sequence numbers 372, 361, 373, 369, 370, and 371, ff) Sequence numbers 374, 375, 376, 377, 378, and 379, gg) Sequence numbers 380, 381, 382, ​​383, 384, and 385, hh) Sequence IDs 926, 927, 928, 929, 930, and 931, ii) Sequence IDs 932, 933, 934, 935, 936, and 937, jj) Sequence IDs 938, 939, 940, 941, 942, and 943, or kk) A multispecific antigen-binding molecule as described in any one of items 1-54, 58-69, and 89-94, including SEQ ID NOs: 944, 945, 946, 947, 948, and 949. (Item 96) The second antigen-binding domain comprises a second VH containing a second VH-CDR1, a second VH-CDR2, and a second VH-CDR3, and a second VL containing a second VL-CDR1, a second VL-CDR2, and a second VH-CDR3, each having the following amino acid sequence (according to IMGT): a) Sequence IDs 386, 387, 388, 389, 239, and 81, b) Sequence IDs 390, 391, 392, 393, 239, and 87, c) Sequence IDs 390, 391, 394, 393, 239, and 87, d) Sequence numbers 395, 396, 397, 393, 239, and 87, e) Sequence IDs 398, 399, 400, 401, 239, and 95, f) Sequence IDs 398, 399, 402, 401, 239, and 95, g) Sequence IDs 403, 404, 405, 406, 258, and 102, h) Sequence IDs 407, 408, 409, 410, 239, and 107, i) Sequence IDs 411, 412, 413, 414, 269, and 113, j) Sequence IDs 415, 416, 417, 418, 275, and 119, k) Sequence IDs 415, 419, 420, 421, 275, and 123, l) Sequence IDs 422, 423, 424, 425, 275, and 113, m) Sequence IDs 426, 416, 427, 425, 275, and 113, n) Sequence IDs 428, 429, 430, 431, 291, and 137, o) Sequence IDs 432, 433, 434, 435, 297, and 143, p) Sequence IDs 436, 437, 438, 439, 303, and 143, q) Sequence IDs 440, 437, 441, 442, 307, and 143, r) Sequence IDs 443, 444, 445, 446, 312, and 159, s) Sequence IDs 447, 448, 449, 450, 318, and 165, t) Sequence IDs 451, 448, 452, 450, 318, and 165, u) Sequence IDs 453, 454, 455, 456, 326, and 173, v) Sequence IDs 453, 457, 455, 456, 326, and 173, w) Sequence IDs 458, 459, 460, 456, 326, and 173, x) Sequence IDs 461, 462, 463, 464, 335, and 183, y) Sequence IDs 465, 466, 467, 468, 341, and 189, z) Sequence IDs 469, 470, 471, 472, 341, and 195, aa) Column numbers 473, 474, 475, 476, 352, and 201, bb) Column numbers 477, 478, 479, 480, 358, and 207, cc) Column numbers 481, 482, 483, 484, 364, and 213, dd) Column numbers 485, 486, 487, 488, 370, and 219, ee) Column numbers 485, 482, 487, 488, 370, and 219, ff) Column numbers 489, 482, 490, 488, 370, and 219, gg) Column numbers 491, 492, 493, 494, 378, and 228, hh) Column numbers 495, 496, 497, 498, 384, and 234, ii) Column numbers 950, 951, 952, 953, 930, and 907, jj) Column numbers 954, 955, 956, 957, 936, and 913, kk) Column numbers 958, 959, 960, 961, 942, and 919, or ll) A multispecific antigen-binding molecule as described in any one of items 1-54, 58-69, and 89-95, including column numbers 962, 963, 964, 965, 948, and 925. (Item 97) The second antigen-binding domain comprises a second VH containing a second VH-CDR1, a second VH-CDR2, and a second VH-CDR3, and a second VL containing a second VL-CDR1, a second VL-CDR2, and a second VH-CDR3, each having the following amino acid sequence (according to Honegger): a) Sequence IDs 499, 500, 501, 238, 502, and 240, b) Sequence IDs 499, 503, 501, 238, 502, and 240, c) Sequence IDs 505, 506, 507, 244, 502, and 245, d) Sequence IDs 508, 509, 510, 244, 502, and 245, e) Sequence IDs 511, 512, 513, 251, 514, and 252, f) Sequence IDs 511, 512, 515, 251, 514, and 252, g) Sequence IDs 516, 517, 518, 257, 519, and 259, h) Sequence IDs 520, 521, 522, 264, 523, and 264, i) Sequence IDs 524, 525, 526, 268, 527, and 270, j) Sequence IDs 528, 529, 530, 274, 531, and 270, k) Sequence IDs 528, 532, 533, 278, 531, and 279, l) Sequence IDs 534, 535, 536, 283, 537, and 270, m) Sequence IDs 1090, 529, 538, 283, 531, and 270, n) Sequence IDs 539, 540, 541, 290, 542, and 292, o) Sequence IDs 543, 544, 545, 546, 547, and 298, p) Sequence IDs 548, 549, 550, 1091, 551, and 298, q) Sequence IDs 552, 553, 554, 555, 556, and 298, r) Sequence IDs 557, 558, 559, 311, 560, and 313, s) Sequence IDs 561, 562, 563, 564, 565, and 165, t) Sequence IDs 566, 562, 1092, 564, 567, and 165, u) Sequence IDs 568, 569, 570, 571, 572, and 327, v) Sequence IDs 568, 573, 570, 571, 572, and 327, w) Sequence numbers 574, 575, 576, 571, 572, and 327, x) Sequence numbers 577, 578, 579, 580, 581, and 336, y) Sequence numbers 582, 583, 584, 340, 585, and 342, z) Sequence numbers 586, 587, 588, 346, 589, and 347, aa) Sequence IDs 590, 591, 592, 351, 593, and 353, bb) Sequence IDs 594, 595, 596, 597, 598, and 359, cc) Sequence IDs 599, 600, 601, 602, 603, and 365, dd) Sequence IDs 604, 605, 606, 607, 608, and 371, ee) Sequence IDs 604, 609, 606, 607, 608, and 371, ff) Sequence IDs 610, 609, 611, 607, 608, and 371, gg) Sequence numbers 612, 613, 614, 615, 616, and 379, hh) Sequence IDs 617, 618, 619, 620, 621, and 385, ii) Sequence IDs 966, 967, 968, 969, 970, and 931, jj) Sequence IDs 971, 972, 973, 974, 975, and 937, kk) Sequence IDs 976, 977, 978, 941, 979, and 943, or ll) A multispecific antigen-binding molecule as described in any one of items 1-54, 58-69, and 89-96, including SEQ ID NOs: 980, 981, 982, 983, 984, and 949. (Item 98) A multispecific antigen-binding molecule according to any one of items 1-54, 58-69, and 89-97, wherein the second VH and the second VL each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: a) Sequence IDs 622 and 623, b) Sequence IDs 624 and 625, c) Sequence IDs 624 and 626, d) Sequence IDs 627 and 628, e) Sequence IDs 629 and 630, f) Sequence IDs 631 and 632, g) Sequence IDs 633 and 634, h) Sequence IDs 635 and 636, i) Sequence IDs 637 and 638, j) Sequence IDs 639 and 640, k) Sequence IDs 641 and 642, l) Sequence IDs 643 and 644, m) Sequence IDs 645 and 646, n) Sequence IDs 647 and 648, o) Sequence IDs 649 and 650, p) Sequence IDs 651 and 652, q) Sequence IDs 653 and 654, r) Sequence IDs 655 and 656, s) Sequence IDs 657 and 658, t) Sequence IDs 659 and 660, u) Sequence IDs 661 and 662, v) Sequence IDs 663 and 664, w) Sequence IDs 665 and 666, x) Sequence IDs 667 and 668, y) Sequence IDs 669 and 670, z) Sequence IDs 671 and 672, aa) Sequence IDs 673 and 670, bb) Sequence IDs 674 and 675, cc) Sequence IDs 676 and 677, dd) Sequence IDs 678 and 679, ee) Sequence IDs 680 and 681, ff) Sequence numbers 682 and 683, gg) Sequence IDs 684 and 685, hh) Sequence IDs 686 and 687, ii) Sequence IDs 688 and 689, jj) Sequence IDs 690 and 691, kk) Sequence IDs 692 and 693, ll) Sequence IDs 694 and 695, mm) Sequence numbers 985 and 986, nn) Sequence IDs 987 and 988, oo) Sequence numbers 989 and 990, or pp) Sequence IDs 991 and 992. (Item 99) The second VH and the second VL each contain an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below, and the following amino acids are present at the positions shown below (position numbering follows Kabat): (i) Sequence IDs 622, 624, or 627, which include one of the following: Ser-Ser-Val (SSV) or Thr-Gly-Val (TGV) at positions 82a-82c, Gln (Q) at position 39, Asn (N) at position 60, His (H) at position 68, Lys (K), His (H), or Thr (T) at position 105, and one or more of the following: Leu (L) at position 2, Ala (A) at position 32, and Ala (A) at position 95; and Sequence IDs 623, 625, 626, or 628, which include one or more of the following: Gly (G) at position 67, Tyr (Y), Phe (F), or Thr (T) at position 67a, Arg (R) at position 67b, Pro (P) at position 67c, and Lys (K) at position 103, or (ii) His (H) in 3rd place, Ser (S) or Val (V) in 5th place, Glu (E) in 10th place, Lys (K) in 12th place, Lys (K) in 23rd place, Asn (N) in 28th place, Arg (R) in 30th place, Tyr (Y) in 32nd place, Thr (T) in 68th place, Met (M) in 69th place, Gln (Q) or His (H) in 72nd place, Tyr (Y) in 74ath place, Phe Sequence numbers 663, 665, or 667, and one or more of the following: (F), Phe(F) or Ser(S) at position 76, Ser(S) at position 77, Ala(A) at position 78, Ser(S) at position 82a, Arg(R) at position 82b, Val(V) at position 82c, Ile(I) or Thr(T) at position 89, Phe(F) at position 98, Tyr(Y) or Gly(G) at position 99, Gln(Q) at position 105, Met(M) at position 108, Phe-Asp-Phe-Asp(FDFD) (Sequence number 1040) at positions 74a, 74b, 74c, and 74d, and Trp-Asp-Phe-Asp(WDFD) (Sequence number 1042) at positions 74a, 74b, 74c, and 74d. A multispecific antigen-binding molecule described in any one of items 1-54, 58-69, and 89-98, including sequence number 664, 666, or 668, which contains one or more of the following: Arg(R) at position 14, Arg(R) at position 18, Ala(A) at position 19, Lys(L) at position 39, Pro(P) at position 40, Thr(T) at position 56, Ala(A) at position 60, Ser(S) at position 65, Thr(T) or His(H) at position 72, Lys(K) at position 74, Ser(S) at position 76, Ser(S) at position 77, Val(V) at position 83, Ile(I) or Phe(F) at position 98, Thr(T) or Gly(G) at position 99, Asn(N) at position 103, and Ile(I) at position 106, including sequence number 664, 666, or 668. (Item 100) The second VH and the second VL each contain an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below, and the following amino acids are present at the positions shown below (position numbering follows Kabat): (i) Sequence IDs 622, 624, or 627 containing one or more of the following: Thr-Gly-Val (TGV) at positions 82a-82c, Asn (N) at position 60, His (H) at position 68, Lys (K), His (H), and Thr (T) at position 105, and Sequence IDs 623, 625, 626, or 628 containing one or more of the following: Gly (G) at position 67, Tyr (Y), Phe (F), or Thr (T) at position 67a, Arg (R) at position 67b, or Pro (P) at position 67c, or (ii) A multispecific antigen-binding molecule according to any one of items 1-54, 58-69, and 89-99, comprising SEQ ID NOs. 663, 665, or 667, which contains Phe(F) at position 74a, and SEQ ID NOs. 664, 666, or 668, which contains Ala(A) at position 19. (Item 101) A multispecific antigen-binding molecule according to any one of items 1 to 100, comprising a heterodimer human IgG1 or IgG4, comprising a first Fc region and a second Fc region. (Item 102) A multispecific antigen-binding molecule as described in item 101, wherein the first Fc region and the second Fc region are derived from IgG1m17. (Item 103) A heterodimer human IgG1 or IgG4 comprising a first Fc region and a second Fc region, wherein one or both of the first and second Fc regions contain the following amino acids at the positions indicated below (EU numbering): (i) Alanine, ranked 234th (ii) Alanine at position 235, and (iii) A multispecific antigen-binding molecule described in any one of items 1 to 102, comprising one or more serine molecules at position 331. (Item 104) A heterodimer human IgG1 or IgG4 comprising a first Fc region and a second Fc region, wherein one or both of the first and second Fc regions contain the following amino acids at the positions indicated below (EU numbering): (i) Tyrosine at position 252, threonine at position 254, and glutamic acid (YTE) at position 256, or (ii) A multispecific antigen-binding molecule according to any one of items 1 to 103, comprising leucine at position 428 and serine (LS) at position 434. (Item 105) A multispecific antigen-binding molecule according to any one of items 1 to 104, comprising a heterodimer human IgG1 including a first Fc region and a second Fc region, wherein both the first and second Fc regions contain the following amino acids at the positions indicated below (EU numbering): tyrosine at position 252, threonine at position 254, and glutamic acid (YTE) at position 256. (Item 106) The first Fc region and the second Fc region contain the following amino acids at the positions shown below (EU numbering): (i) The first Fc region comprises tryptophan at position 366 (T366W), and the second Fc region comprises serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V); (ii) The first Fc region comprises serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V), and the second Fc region comprises tryptophan at position 366 (T366W); (iii) The first Fc region comprises cysteine ​​at position 354 (S354C) and tryptophan at position 366 (T366W), and the second Fc region comprises cysteine ​​at position 349 (Y349C), serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V); (iv) A multispecific antigen-binding molecule according to any one of items 1 to 105, comprising a first Fc region and a second Fc region, wherein the first Fc region comprises cysteine ​​at position 349 (Y349C), serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V), and the second Fc region comprises cysteine ​​at position 354 (S354C) and tryptophan at position 366 (T366W), comprising a heterodimer human IgG1 or IgG4. (Item 107) A multispecific antigen-binding molecule according to any one of items 1 to 106, comprising a first Fc region and a second Fc region containing the following amino acids at the positions indicated below (EU numbering), wherein the first Fc region contains serine (T366S) at position 366, alanine (L368A) at position 368, and valine (Y407V) at position 407, and the second Fc region contains tryptophan (T366W) at position 366, comprising a first Fc region and a second Fc region. (Item 108) A multispecific antigen-binding molecule according to any one of items 1 to 107, comprising a heterodimer human IgG1 or IgG4 including a first hinge region and a second hinge region, wherein one or both of the first and second hinge regions contain serine (C220S) (EU numbering) at position 220. (Item 109) A heterodimer human IgG1 or IgG4 comprising a first Fc region and a second Fc region, wherein one of the first or second Fc region contains the following amino acids at the position indicated below (EU numbering): (i) Arginine at position 435 (H435R), or (ii) A multispecific antigen-binding molecule as described in any one of items 1 to 108, comprising arginine at position 435 (H435R) and phenylalanine at position 436 (Y436F). (Item 110) A multispecific antigen-binding molecule according to any one of items 1 to 109, comprising a heterodimer human IgG1 including a first Fc region and a second Fc region, wherein the first Fc region contains the following amino acid at the position shown below (EU numbering): arginine at position 435 (H435R). (Item 111) The first Fc region and the second Fc region contain the following amino acids at the positions shown below (EU numbering): (i) The first Fc region comprises alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), and tryptophan at position 366 (T366W), and the second Fc region comprises alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), serine at position 366 (T366S), alanine at position 368 (L368A), valine at position 407 (Y407V), and arginine at position 435 (H435R); (ii) The first Fc region comprises alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), and tryptophan at position 366 (T366W), and the second Fc region comprises alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), serine at position 366 (T366S), alanine at position 368 (L368A), valine at position 407 (Y407V), arginine at position 435 (H435R), and phenylalanine at position 436 (Y436F); (iii) The first Fc region comprises alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), serine at position 366 (T366S), alanine at position 368 (L368A), and valine at position 407 (Y407V), and the second Fc region comprises alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), and tryptophan at position 366 (T366W); (iv) The first Fc region comprises alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), tryptophan at position 366 (T366W), leucine at position 428 (M428L), and serine at position 434 (N434S), and the second Fc region comprises alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), serine at position 366 (T366S), alanine at position 368 (L368A), valine at position 407 (Y407V), and arginine at position 435 (H435R); or (v) The first Fc region includes alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), tryptophan at position 366 (T366W), tyrosine at position 252 (M252Y), threonine at position 254 (S254T), and glutamic acid at position 256 (T256E), and the second Fc region includes alanine at position 234 (L234), position 235 A multispecific antigen-binding molecule according to any one of items 1 to 110, comprising a heterodimer human IgG1 or IgG4, comprising a first Fc region and a second Fc region, the first Fc region comprising alanine (L235A), serine (P331S) at position 331, serine (T366S) at position 366, alanine (L368A) at position 368, valine (Y407V) at position 407, and arginine (H435R) at position 435. (Item 112) A first Fc region and a second Fc region containing the following amino acids at the positions shown below (EU numbering), wherein the first Fc region contains alanine (L234) at position 234, alanine (L235A) at position 235, serine (P331S) at position 331, serine (T366S) at position 366, alanine (L368A) at position 368, valine (Y407V) at position 407, and arginine (H435R) at position 435, and the second Fc region is A multispecific antigen-binding molecule according to any one of items 1 to 111, comprising a heterodimer human IgG1 comprising a first Fc region and a second Fc region, the first Fc region comprising alanine at position 234 (L234), alanine at position 235 (L235A), serine at position 331 (P331S), tryptophan at position 366 (T366W), tyrosine at position 252 (M252Y), threonine at position 254 (S254T), and glutamic acid at position 256 (T256E). (Item 113) A multispecific antigen-binding molecule according to any one of items 1 to 112, comprising a first Fc region and a second Fc region, each containing the amino acid sequence shown below, or each containing an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: a) Sequence IDs 696 and 697, b) Sequence IDs 697 and 696, c) Sequence IDs 696 and 698, d) Sequence IDs 698 and 696, e) Sequence IDs 699 and 700, f) Sequence IDs 700 and 699, g) Sequence IDs 701 and 698, h) Sequence IDs 698 and 701, i) Sequence IDs 702 and 703, j) Sequence IDs 703 and 702, k) Sequence IDs 704 and 698, l) Sequence IDs 698 and 704, m) Sequence IDs 705 and 703, n) Sequence IDs 703 and 705, o) Sequence IDs 706 and 704, p) Sequence IDs 704 and 706, q) Sequence IDs 707 and 703, r) Sequence IDs 703 and 707, s) Sequence IDs 708 and 704, t) Sequence IDs 704 and 708, u) Sequence IDs 709 and 710, or v) Sequence IDs 710 and 709. (Item 114) A multispecific antigen-binding molecule according to any one of items 1 to 113, comprising a heterodimer human IgG1 comprising a first Fc region and a second Fc region, each comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequences shown in SEQ ID NOs. 703 and 705, respectively. (Item 115) A multispecific antigen-binding molecule according to any one of items 1 to 114, comprising a heterodimer human IgG1, comprising a first Fc region and a second Fc region, each comprising an amino acid sequence that is at least 95% identical to the amino acid sequences shown in SEQ ID NOs. 703 and 705, respectively. (Item 116) A multispecific antigen-binding molecule according to any one of items 1 to 115, comprising a heterodimer human IgG1, comprising a first Fc region and a second Fc region, each comprising an amino acid sequence that is at least 99% identical to the amino acid sequences shown in SEQ ID NOs. 703 and 705, respectively. (Item 117) A multispecific antigen-binding molecule according to any one of items 1 to 116, comprising heterodimer human IgG1, each containing the amino acid sequences shown in SEQ ID NOs. 703 and 705, respectively. (Item 118) The first antigen-binding domain is a scFv, the second antigen-binding domain is a Fab, the first antigen-binding domain contains a first heavy chain (HC), the second antigen-binding domain contains a second HC and a light chain (LC), and the first HC, the second HC, and the LC each contain the amino acid sequences shown below, or each contain amino acid sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequences shown below. The multispecific antigen-binding molecule according to any one of items 1 to 117: 1) SEQ ID NOs: 800, 801, and 802, 2) SEQ ID NOs: 800, 803, and 802, 3) SEQ ID NOs: 804, 803, and 802, 4) SEQ ID NOs: 804, 805, and 802, 5) SEQ ID NOs: 806, 801, and 802, 6) SEQ ID NOs: 806, 803, and 802, 7) SEQ ID NOs: 807, 803, and 802, 8) SEQ ID NOs: 807, 805, and 802, 9) SEQ ID NOs: 808, 809, and 802, 10) SEQ ID NOs: 808, 810, and 802, 11) SEQ ID NOs: 811, 801, and 802, 12) SEQ ID NOs: 812, 809, and 802, 13) SEQ ID NOs: 812, 810, and 802, 14) SEQ ID NOs: 813, 805, and 802, 15) SEQ ID NOs: 812, 814, and 802, 16) SEQ ID NOs: 815, 801, and 802, 17) SEQ ID NOs: 816, 805, and 802, 18) SEQ ID NOs: 817, 801, and 802, 19) SEQ ID NOs: 818, 805, and 802, 20) SEQ ID NOs: 819, 810, and 802, 21) SEQ ID NO: 820, 810, and 802, 22) SEQ ID NO: 821, 822, and 823, 23) SEQ ID NO: 824, 825, and 823, 24) SEQ ID NO: 826, 825, and 823, 25) SEQ ID NO: 826, 827, and 823, 26) SEQ ID NO: 828, 829, and 823, 27) SEQ ID NO: 830, 822, and 823, 28) SEQ ID NO: 830, 825, and 823, 29) SEQ ID NO: 831, 825, and 823, 30) SEQ ID NO: 831, 827, and 823, 31) SEQ ID NO: 832, 833, and 823, 32) SEQ ID NO: 832, 829, and 823, 33) SEQ ID NO: 834, 827, and 823, 34) SEQ ID NO: 835, 829, and 823, 35) SEQ ID NO: 836, 829, and 823, 36) SEQ ID NO: 837, 833, and 823, 37) SEQ ID NO: 837, 838, and 823, 38) SEQ ID NO: 839, 840, and 823, 39) SEQ ID NO: 841, 829, and 823, 40) SEQ ID NO: 842, 829, and 823, 41) SEQ ID NO: 843, 829, and 823, 42) SEQ ID NO: 844, 829, and 823, 43) SEQ ID NO: 845, 829, and 823, 44) SEQ ID NO: 846, 829, and 823, 45) SEQ ID NO: 846, 833, and 823, 46) SEQ ID NO: 846, 838, and 823, 47) SEQ ID NO: 847, 827, and 823, 48) SEQ ID NO: 848, 829, and 823, 49) SEQ ID NO: 849, 829, and 823, 50) Sequence IDs 850, 829, and 823, 51) Sequence IDs 851, 829, and 823, 52) Sequence IDs 852, 829, and 823, 53) Sequence IDs 853, 829, and 823, 54) Sequence IDs 854, 829, and 823, 55) Sequence IDs 855, 829, and 823, 56) Sequence IDs 856, 829, and 823, 57) Sequence IDs 857, 829, and 823, 58) Sequence IDs 858, 829, and 823, 59) Sequence IDs 859, 829, and 823, 60) Sequence IDs 860, 829, and 823, 61) Sequence IDs 861, 862, and 863, 62) Sequence IDs 861, 864, and 863, 63) Sequence IDs 865, 864, and 863, 64) Sequence IDs 865, 866, and 863, 65) Sequence IDs 867, 868, and 863, 66) Sequence IDs 869, 862, and 863, 67) Sequence IDs 869, 864, and 863, 68) Sequence IDs 870, 864, and 863, 69) Sequence IDs 870, 866, and 863, 70) Sequence IDs 871, 872, and 863, 71) Sequence IDs 871, 868, and 863, 72) Sequence IDs 873, 862, and 863, 73) Sequence IDs 874, 866, and 863, 74) Sequence IDs 875, 872, and 863, 75) Sequence IDs 875, 868, and 863, 76) Sequence IDs 875, 876, and 863, 77) Sequence IDs 877, 862, and 863, 78) Sequence numbers 878, 866, and 863, 79) SEQ ID NOs: 879, 862, and 863, 80) SEQ ID NOs: 880, 866, and 863, 81) SEQ ID NOs: 881, 882, and 883, 82) SEQ ID NOs: 881, 884, and 883, 83) SEQ ID NOs: 885, 884, and 883, 84) SEQ ID NOs: 885, 886, and 883, 85) SEQ ID NOs: 887, 888, and 883, 86) SEQ ID NOs: 889, 882, and 883, 87) SEQ ID NOs: 889, 884, and 883, 88) SEQ ID NOs: 890, 884, and 883, 89) SEQ ID NOs: 890, 886, and 883, 90) SEQ ID NOs: 891, 892, and 883, 91) SEQ ID NOs: 891, 888, and 883, 92) SEQ ID NOs: 893, 882, and 883, 93) SEQ ID NOs: 894, 886, and 883, 94) SEQ ID NOs: 895, 892, and 883, 95) SEQ ID NOs: 895, 888, and 883, 96) SEQ ID NOs: 895, 896, and 883, 97) SEQ ID NOs: 897, 882, and 883, 98) SEQ ID NOs: 898, 886, and 883, 99) SEQ ID NOs: 899, 882, and 883, or 100) SEQ ID NOs: 900, 886, and 883. (Item 119) A multispecific antigen-binding molecule according to any one of items 1 to 118, wherein the first antigen-binding domain is scFv, the second antigen-binding domain is Fab, the first antigen-binding domain comprises a first heavy chain (HC), the second antigen-binding domain comprises a second HC and a light chain (LC), and the first HC, the second HC, and the LC each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: 1) Sequence IDs 800, 801, and 802, 2) Sequence IDs 800, 803, and 802, 3) Sequence IDs 804, 803, and 802, 4) Sequence IDs 804, 805, and 802, 5) Sequence IDs 806, 801, and 802, 6) Sequence IDs 806, 803, and 802, 7) Sequence IDs 807, 803, and 802, 8) Sequence IDs 807, 805, and 802, 9) Sequence IDs 808, 809, and 802, 10) Sequence IDs 808, 810, and 802, 11) Sequence IDs 821, 822, and 823, 12) Sequence IDs 824, 825, and 823, 13) Sequence IDs 826, 825, and 823, 14) Sequence IDs 826, 827, and 823, 15) Sequence IDs 828, 829, and 823, 16) Sequence IDs 830, 822, and 823, 17) Sequence IDs 830, 825, and 823, 18) Sequence IDs 831, 825, and 823, 19) Sequence IDs 831, 827, and 823, 20) Sequence IDs 832, 833, and 823, 21) Sequence IDs 832, 829, and 823, 22) Sequence IDs 861, 862, and 863, 23) Sequence IDs 861, 864, and 863, 24) Sequence IDs 865, 864, and 863, 25) Sequence IDs 865, 866, and 863, 26) Sequence numbers 867, 868, and 863, 27) Sequence IDs 869, 862, and 863, 28) Sequence IDs 869, 864, and 863, 29) Sequence IDs 870, 864, and 863, 30) Sequence IDs 870, 866, and 863, 31) Sequence IDs 871, 872, and 863, 32) Sequence IDs 871, 868, and 863, 33) Sequence numbers 881, 882, and 883, 34) Sequence IDs 881, 884, and 883, 35) Sequence IDs 885, 884, and 883, 36) Sequence IDs 885, 886, and 883, 37) Sequence numbers 887, 888, and 883, 38) Sequence IDs 889, 882, and 883, 39) Sequence IDs 889, 884, and 883, 40) Sequence IDs 890, 884, and 883, 41) Sequence IDs 890, 886, and 883, 42) Sequence IDs 891, 892, and 883, or 43) Sequence IDs 891, 888, and 883. (Item 120) A multispecific antigen-binding molecule according to any one of items 1 to 119, wherein the first antigen-binding domain is scFv, the second antigen-binding domain is Fab, the first antigen-binding domain comprises a first heavy chain (HC), the second antigen-binding domain comprises a second HC and a light chain (LC), and the first HC, the second HC, and the LC each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: 1) Sequence IDs 800, 801, and 802, 2) Sequence IDs 800, 803, and 802, 3) Sequence IDs 804, 803, and 802, 4) Sequence IDs 804, 805, and 802, 5) Sequence IDs 821, 822, and 823, 6) Sequence IDs 824, 825, and 823, 7) Sequence IDs 826, 825, and 823, 8) Sequence IDs 826, 827, and 823, 9) Sequence IDs 828, 829, and 823, 10) Sequence IDs 861, 862, and 863, 11) Sequence IDs 861, 864, and 863, 12) Sequence IDs 865, 864, and 863, 13) Sequence IDs 865, 866, and 863, 14) Sequence IDs 867, 868, and 863, 15) Sequence IDs 881, 882, and 883, 16) Sequence IDs 881, 884, and 883, 17) Sequence IDs 885, 884, and 883, 18) Sequence IDs 885, 886, and 883, or 19) Sequence numbers 887, 888, and 883. (Item 121) A multispecific antigen-binding molecule according to any one of items 1 to 120, wherein the first antigen-binding domain is scFv, the second antigen-binding domain is Fab, the first antigen-binding domain comprises a first heavy chain (HC), the second antigen-binding domain comprises a second HC and a light chain (LC), and the first HC, the second HC, and the LC each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: 1) Sequence IDs 800, 801, and 802, 2) Sequence IDs 800, 803, and 802, 3) Sequence IDs 804, 803, and 802, 4) Sequence IDs 804, 805, and 802, 5) Sequence IDs 821, 822, and 823, 6) Sequence IDs 824, 825, and 823, 7) Sequence IDs 826, 825, and 823, 8) Sequence IDs 826, 827, and 823, 9) Sequence IDs 828, 829, and 823, 10) Sequence IDs 861, 862, and 863, 11) Sequence IDs 861, 864, and 863, 12) Sequence IDs 865, 864, and 863, 13) Sequence IDs 865, 866, and 863, or 14) Sequence IDs 867, 868, and 863. (Item 122) A multispecific antigen-binding molecule that binds to human CD3 and HIV gp120, wherein the antigen-binding molecule is (a) A first antigen-binding domain comprising a first heavy chain variable domain (VH) and a first light chain variable domain (VL), wherein the first antigen-binding domain binds to CD3, (b) A multispecific antigen-binding molecule comprising: a second antigen-binding domain that binds to HIV gp120, comprising one or more extracellular (EC) domains of CD4, wherein one or more EC domains of CD4 contain a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the sequences shown below or selected from the group consisting of the following: (i)KKVVYGKKGDTVELTCTASQKKNIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRVDSRRSLWDQGNFPLIIKNLKPEDSDTYICEVEDQKEEVQLVVVG (Sequence ID 746), (ii) KKVVYGKKGDTVELTCTASQKKNIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRVDSRRSLWDQGNFPLIIKNLKPEDSDTYICEVEDQKEEVQLVVVGGGGSGKKVVYGKKGDTVELTCTASQKKNIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRVDSRRSLWDQGNFPLIIKNLKPEDSDTYICEVEDQKEEVQLVVVG (Sequence ID 747), (iii)KKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQLLVFG (Sequence ID 748), or (iv)KKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQLLVFGGGGSGKKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQLLVFG (Sequence ID 749). (Item 123) The multispecific antigen-binding molecule described in item 122: SEQ ID NO: 746, wherein one or more EC domains of the CD4 contain the sequence shown below, or a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the sequence shown below. (Item 124) A multispecific antigen-binding molecule according to any one of items 1-88, 101-117, and 122-123, wherein the first antigen-binding domain is Fab, the second antigen-binding domain is the EC domain of scFv or CD4, the first antigen-binding domain comprises a first HC and LC, the second antigen-binding domain comprises a second HC, and the second HC, the first HC, and the LC each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: 1) Sequence IDs 751, 752, and 753, 2) Sequence IDs 754, 752, and 753, 3) Sequence IDs 755, 756, and 753, 4) Sequence IDs 755, 757, and 753, 5) Sequence IDs 758, 757, and 753, 6) Sequence IDs 759, 756, and 753, 7) Sequence IDs 754, 760, and 761, 8) Sequence IDs 762, 760, and 761, 9) Sequence IDs 751, 763, and 753, 10) Sequence IDs 764, 752, and 753, 11) Sequence IDs 765, 752, and 753, 12) Sequence IDs 766, 767, and 753, 13) Sequence IDs 766, 768, and 753, 14) Sequence IDs 769, 768, and 753, 15) Sequence IDs 770, 767, and 753, 16) Sequence IDs 765, 771, and 761, 17) Sequence IDs 772, 771, and 761, 18) Sequence IDs 774, 775, and 776, 19) Sequence IDs 777, 778, and 776, 20) Sequence IDs 779, 778, and 776, 21) Sequence IDs 779, 780, and 776, 22) Sequence IDs 777, 781, and 776, 23) Sequence IDs 782, 752, and 753, 24) Sequence IDs 783, 752, and 753, 25) Sequence IDs 784, 785, and 753, 26) Sequence IDs 784, 786, and 753, 27) Sequence IDs 787, 786, and 753, 28) Sequence IDs 788, 785, and 753, 29) Sequence IDs 783, 789, and 761, 30) Sequence IDs 790, 789, and 761, 31) Sequence IDs 792, 793, and 794, 32) Sequence IDs 795, 796, and 794, 33) Sequence IDs 797, 796, and 794, 34) Sequence IDs 797, 798, and 794, or 35) Sequence IDs 795, 799, and 794. (Item 125) A multispecific antigen-binding molecule according to any one of items 1-88, 101-117, and 122-124, wherein the first antigen-binding domain is Fab, the second antigen-binding domain is the EC domain of scFv or CD4, the first antigen-binding domain comprises a first HC and LC, the second antigen-binding domain comprises a second HC, and the second HC, the first HC, and the LC each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: 1) Sequence IDs 751, 752, and 753, 2) Sequence IDs 754, 752, and 753, 3) Sequence IDs 755, 756, and 753, 4) Sequence IDs 755, 757, and 753, 5) Sequence IDs 758, 757, and 753, 6) Sequence IDs 759, 756, and 753, 7) Sequence IDs 764, 752, and 753, 8) Sequence IDs 765, 752, and 753, 9) Sequence IDs 766, 767, and 753, 10) Sequence IDs 766, 768, and 753, 11) Sequence IDs 769, 768, and 753, 12) Sequence IDs 770, 767, and 753, 13) Sequence IDs 777, 778, and 776, 14) Sequence IDs 779, 778, and 776, 15) Sequence IDs 779, 780, and 776, 16) Sequence IDs 777, 781, and 776, 17) Sequence IDs 782, 752, and 753, 18) Sequence IDs 783, 752, and 753, 19) Sequence IDs 784, 785, and 753, 20) Sequence IDs 784, 786, and 753, 21) Sequence IDs 787, 786, and 753, 22) Sequence IDs 788, 785, and 753, 23) Sequence IDs 795, 796, and 794, 24) Sequence IDs 797, 796, and 794, 25) Sequence IDs 797, 798, and 794, or 26) Sequence IDs 795, 799, and 794. (Item 126) A multispecific antigen-binding molecule according to any one of items 1-88, 101-117, and 122-125, wherein the first antigen-binding domain is Fab, the second antigen-binding domain is the EC domain of scFv or CD4, the first antigen-binding domain comprises a first HC and LC, the second antigen-binding domain comprises a second HC, and the second HC, the first HC, and the LC each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: 1) Sequence IDs 751, 752, and 753, 2) Sequence IDs 754, 752, and 753, 3) Sequence IDs 755, 756, and 753, 4) Sequence IDs 755, 757, and 753, 5) Sequence IDs 758, 757, and 753, or 6) Sequence IDs 759, 756, and 753. (Item 127) A multispecific antigen-binding molecule according to any one of items 1-88, 101-117, and 122-126, wherein the first antigen-binding domain is Fab, the second antigen-binding domain is the EC domain of scFv or CD4, the first antigen-binding domain comprises a first HC and LC, the second antigen-binding domain comprises a second HC, and the second HC, the first HC, and the LC each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: 1) Sequence IDs 751, 752, and 753, or 2) Sequence IDs 755, 756, and 753. (Item 128) A multispecific antigen-binding molecule according to any one of items 1-88, 101-117, and 122-127, wherein the first antigen-binding domain is Fab, the second antigen-binding domain is the EC domain of CD4, the first antigen-binding domain comprises a first HC and LC, the second antigen-binding domain comprises a second HC, and the second HC, the first HC, and the LC each contain an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the following amino acid sequences: SEQ ID NOs: 751, 752, and 753. (Item 129) A multispecific antigen-binding molecule according to any one of items 1-88, 101-117, and 122-128, wherein the first antigen-binding domain is Fab, the second antigen-binding domain is the EC domain of CD4, the first antigen-binding domain comprises a first HC and LC, the second antigen-binding domain comprises a second HC, and the second HC, the first HC, and the LC each contain an amino acid sequence that is at least 95% identical to the amino acid sequences shown below: SEQ ID NOs: 751, 752, and 753. (Item 130) A multispecific antigen-binding molecule according to any one of items 1-88, 101-117, and 122-129, wherein the first antigen-binding domain is Fab, the second antigen-binding domain is the EC domain of CD4, the first antigen-binding domain comprises a first HC and LC, the second antigen-binding domain comprises a second HC, and the second HC, the first HC, and the LC each contain an amino acid sequence that is at least 99% identical to the amino acid sequences shown below: SEQ ID NOs: 751, 752, and 753. (Item 131) A multispecific antigen-binding molecule according to any one of items 1-88, 101-117, and 122-130, wherein the first antigen-binding domain is Fab, the second antigen-binding domain is the EC domain of CD4, the first antigen-binding domain comprises a first HC and LC, the second antigen-binding domain comprises a second HC, and the second HC, the first HC, and the LC each contain the amino acid sequences shown below: SEQ ID NOs: 751, 752, and 753. (Item 132) The multispecific antigen-binding molecule described in any one of items 1 to 131, wherein the multispecific antigen-binding molecule is a bispecific antigen-binding molecule. (Item 133) A multispecific antigen-binding molecule as described in item 132, which binds to or targets human CD3 and HIV gp120. (Item 134) The multispecific antigen-binding molecule according to any one of items 1 to 133, wherein the first VH and the first VL each have at least 80%, 81%, 82%, 83%, 84%, 85% or more sequence similarity with human germline VH and human germline VL. (Item 135) The multispecific antigen-binding molecule according to any one of items 1 to 134, wherein the binding of the first antigen-binding domain to protein A is reduced, or is slight or substantially absent, or does not detectably bind to protein A. (Item 136) The first antigen-binding domain is 10 -6 M or more of K D to bind to protein A, the multispecific antigen-binding molecule according to any one of items 1 to 134. (Item 137) The first antigen-binding domain binds to CD3 with a K D less than 10 nM, for example, 9.5 nM, 9.0 nM, 8.5 nM, 8.0 nM, 7.5 nM, 7.0 nM, 6.5 nM, 6.0 nM, 5.5 nM, 5.0 nM, 4.5 nM, 4.0 nM, 3.5 nM, less than 3.0 nM, the multispecific antigen-binding molecule according to any one of items 1 to 136. (Item 138) The multispecific antigen-binding molecule according to item 137, wherein the first antigen-binding domain binds to CD3 with a KD less than 3.0 nM (for example, 2.5 nM). (Item 139) The first antigen-binding molecule has a serum half-life of at least 3 days, for example, at least 4 days, at least 5 days, at least 6 days, at least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 15 days, at least 16 days or more in humans or cynomolgus monkeys, the multispecific antigen-binding molecule according to any one of items 1 to 137. (Item 140) The first antigen-binding molecule is a multispecific antigen-binding molecule according to any one of items 1 to 139, wherein the first antigen-binding molecule has a serum half-life of at least 7 days in humans or cynomolgus monkeys. (Item 141) The first antigen-binding domain has a K content of less than 7.0 nM, for example, 6.5 nM, 6.0 nM, 5.5 nM, 5.0 nM, 4.5 nM, 4.0 nM, 3.5 nM, and less than 3.0 nM. D A multispecific antigen-binding molecule according to any one of items 1 to 139, wherein the antigen-binding molecule has a serum half-life in humans or cynomolgus monkeys of at least 5 days, for example, at least 5.5 days, at least 6 days, at least 6.5 days, at least 7 days, at least 7.5 days, at least 8 days, at least 8.5 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, or at least 14 days. (Item 142) A multispecific antigen-binding molecule according to any one of items 1 to 141, wherein the first antigen-binding domain binds to CD3 with a KD of less than 3.0 nM (e.g., 2.5 nM), and the antigen-binding molecule has a serum half-life of at least 7 days in humans or cynomolgus monkeys. (Item 143) A multispecific antigen-binding molecule according to any one of items 1 to 142, wherein at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, and at least 90% of the N-linked glycosylation sites in at least one of the first VH, the first VL, the second VH, and the second VL are sialylated. (Item 144) A multispecific antigen-binding molecule according to any one of items 1 to 143, wherein the N-linked glycosylation site in at least one of the first VH, the first VL, the second VH, and the second VL has a sialic acid occupancy of at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, or at least 90% (e.g., a glycan containing one or two terminal sialic acid residues). (Item 145) The multispecific antigen-binding molecule according to item 143 or 144, wherein the sialylated N-linked glycosylation site in at least one of the first VH, the first VL, the second VH, and the second VL comprises 1 to 5 sialic acid residues, for example, 1 to 4 sialic acid residues, for example, 1 to 3 sialic acid residues, for example, 1 to 2 sialic acid residues. (Item 146) A multispecific antigen-binding molecule according to any one of items 143 to 145, wherein at least one of the first VH, the first VL, the second VH, and the second VL is sialylated with N-acetylneuraminic acid (NANA). (Item 147) A multispecific antigen-binding molecule as described in any one of items 143 to 146, wherein the sialic acid residue is present in a bibranched structure. (Item 148) A multispecific antigen-binding molecule according to any one of items 143 to 147, wherein the sialic acid residue exists in a complex N-linked glycan structure. (Item 149) A multispecific antigen-binding molecule according to any one of items 143 to 147, wherein the sialic acid residue exists in a hybrid N-linked glycan structure. (Item 150) The glycan is terminally sialylated, and the multispecific antigen-binding molecule is one of the items 143 to 147. (Item 151) A polynucleotide or a plurality of polynucleotides encoding the first VH and the first VL of any of the multispecific antigen-binding molecules described in any one of items 1 to 124. (Item 152) A polynucleotide (or multiple polynucleotides) as described in item 151, further comprising a polynucleotide or multiple polynucleotides encoding a second VH and a second VL of a multispecific antigen-binding molecule as described in any one of items 64 to 132. (Item 153) A polynucleotide (or multiple polynucleotides) as described in item 151 or 152, comprising a polynucleotide or multiple polynucleotides encoding the HC of a first antigen-binding domain which is scFv, and the HC and LC of a second antigen-binding domain which is Fab, as described in any one of items 64 to 121. (Item 154) A polynucleotide (or multiple polynucleotides) as described in item 151 or 152, comprising a polynucleotide or multiple polynucleotides encoding the HC and LC of a first antigen-binding domain which is Fab, and the HC of a second antigen-binding domain which is the EC domain of scFv or CD4, of a multispecific antigen-binding molecule described in any one of items 64 to 132. (Item 155) Polynucleotides (multiple) described in any one of items 151 to 154 that encode a multispecific antigen-binding molecule described in any one of items 122 to 132, each containing the following polynucleotide sequences, or polynucleotide sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the polynucleotide sequences shown below: i. Sequence IDs 995, 996, and 997, ii. Sequence IDs 998, 999, and 1000, iii. Sequence IDs 1001, 1002, and 1003, iv. Sequence IDs 1004, 1005, and 1000, v. Sequence IDs 1006, 1002, and 997, vi. Sequence IDs 1007, 1093, and 1000, vii. Sequence IDs 998, 1008, and 1000, viii. Sequence IDs 998, 1009, and 1000, ix. Sequence IDs 1010, 1011, and 1012, x. Sequence IDs 1013, 1014, and 1015, xi. Sequence IDs 1016, 1017, and 1012, xii. Sequence IDs 1018, 1019, and 1012, xiii. Sequence IDs 1018, 1020, and 1012, xiv. Sequence IDs 1021, 1022, and 1023, or xv. Sequence IDs 1024, 1025, and 1023. (Item 156) Polynucleotides (multiple) according to any one of items 151 to 155 that encode a multispecific antigen-binding molecule according to any one of items 122 to 132, comprising the following polynucleotide sequences, or polynucleotide sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the polynucleotide sequences shown below, respectively: SEQ ID NOs: 995, 996, and 997. (Item 157) The polynucleotides(s) listed in item 156, each containing a polynucleotide sequence that is at least 95% identical to the polynucleotide sequence shown below: SEQ ID NOs: 995, 996, and 997. (Item 158) The polynucleotides(s) listed in item 156 or 157, each containing a polynucleotide sequence that is at least 99% identical to the polynucleotide sequence shown below: SEQ ID NOs: 995, 996, and 997. (Item 159) Each of the following polynucleotides contains one or more of the polynucleotides listed in any one of items 156-158: SEQ ID NOs: 995, 996, and 997. (Item 160) Polynucleotides (multiple) according to any one of items 151 to 155 that encode a multispecific antigen-binding molecule according to any one of items 122 to 132, comprising the following polynucleotide sequences, or polynucleotide sequences that are at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the polynucleotide sequences shown below, respectively: SEQ ID NOs: 998, 999, and 1000. (Item 161) The polynucleotides listed in item 156, each containing a polynucleotide sequence that is at least 95% identical to the polynucleotide sequences shown below: SEQ ID NOs: 998, 999, and 1000. (Item 162) The polynucleotides(s) listed in item 156 or 157, each containing a polynucleotide sequence that is at least 99% identical to the polynucleotide sequences shown below: SEQ ID NOs: 998, 999, and 1000. (Item 163) Each of the following polynucleotides contains one of the polynucleotides listed in items 156-158: SEQ ID NOs: 998, 999, and 1000. (Item 164) The polynucleotide(s) mentioned above is a polynucleotide(s) described in any one of items 151 to 163, which is composed of DNA or RNA. (Item 165) The aforementioned polynucleotide(s) is a polynucleotide(s) described in any one of items 151 to 164, wherein the polynucleotide(s) is composed of mRNA. (Item 166) Polynucleotides (or multiple polynucleotides) described in any one of items 151-165, including codon bias, for efficient expression in human cells. (Item 167) Lipoplexes, e.g., lipid nanoparticles (LNPs), comprising one or more polynucleotides as described in any one of items 151-166. (Item 168) An expression cassette or a set of expression cassettes comprising one or more regulatory sequences operably bound to any one of the polynucleotides(s) described in items 151-166. (Item 169) An expression vector or multiple expression vectors comprising one or more control sequences operably bound to any one of the polynucleotides described in items 151 to 166, or to an expression cassette described in item 168. (Item 170) The expression vector(s) described in item 169 includes a plasmid vector or a viral vector. (Item 171) The expression vector (i) A first expression cassette containing a first polynucleotide encoding the anti-HIV gp120 VL-CL fusion protein, (ii) A second expression cassette containing a second polynucleotide encoding an anti-HIV gp120 VH-Fc fusion protein, and (iii) An expression vector according to item 169 or 170, comprising a third expression cassette containing a third polynucleotide encoding an anti-CD3 scFv-Fc fusion protein. (Item 172) The expression vector is expressed in the order from 5' to 3', (i) A first expression cassette containing a first polynucleotide encoding the anti-HIV gp120 VL-CL fusion protein, (ii) A second expression cassette containing a second polynucleotide encoding an anti-HIV gp120 VH-Fc fusion protein, and (iii) An expression vector according to item 169 or 170, comprising a third expression cassette containing a third polynucleotide encoding an anti-CD3 scFv-Fc fusion protein. (Item 173) The expression vector according to item 171 or 172, wherein the anti-HIV gp120 VL-CL fusion protein, the anti-HIV gp120 VH-Fc fusion protein, and the anti-CD3 scFv-Fc fusion protein each contain the amino acid sequence shown below, or each contains an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence shown below: 1) Sequence IDs 802, 801, and 800, 2) Sequence IDs 802, 803, and 800, 3) Sequence IDs 802, 803, and 804, 4) Sequence IDs 802, 805, and 804, 5) Sequence IDs 802, 801, and 806, 6) Sequence IDs 802, 803, and 806, 7) Sequence IDs 802, 803, and 807, 8) Sequence IDs 802, 805, and 807, 9) Sequence IDs 802, 809, and 808, 10) Sequence IDs 802, 810, and 808, 11) Sequence IDs 802, 801, and 811, 12) Sequence IDs 802, 809, and 812, 13) Sequence IDs 802, 810, and 812, 14) Sequence IDs 802, 805, and 813, 15) Sequence IDs 802, 814, and 812, 16) Sequence IDs 802, 801, and 815, 17) Sequence IDs 802, 805, and 816, 18) Sequence IDs 802, 801, and 817, 19) Sequence IDs 802, 805, and 818, 20) Sequence IDs 802, 810, and 819, 21) Sequence IDs 802, 810, and 820, 22) Sequence IDs 823, 822, and 821, 23) Sequence IDs 823, 825, and 824, 24) Sequence IDs 823, 825, and 826, 25) Sequence IDs 823, 827, and 826, 26) Sequence IDs 823, 829, and 828, 27) Sequence IDs 823, 822, and 830, 28) Sequence IDs 823, 825, and 830, 29) Sequence IDs 823, 825, and 831, 30) Sequence IDs 823, 827, and 831, 31) Sequence IDs 823, 833, and 832, 32) Sequence IDs 823, 829, and 832, 33) Sequence IDs 823, 827, and 834, 34) Sequence IDs 823, 829, and 835, 35) Sequence IDs 823, 829, and 836, 36) Sequence IDs 823, 833, and 837, 37) Sequence IDs 823, 838, and 837, 38) Sequence IDs 823, 840, and 839, 39) Sequence IDs 823, 829, and 841, 40) Sequence IDs 823, 829, and 842, 41) Sequence IDs 823, 829, and 843, 42) Sequence IDs 823, 829, and 844, 43) Sequence IDs 823, 829, and 845, 44) Sequence IDs 823, 829, and 846, 45) Sequence IDs 823, 833, and 846, 46) Sequence IDs 823, 838, and 846, 47) Sequence IDs 823, 827, and 847, 48) Sequence IDs 823, 829, and 848, 49) Sequence IDs 823, 829, and 849, 50) Sequence IDs 823, 829, and 850, 51) Sequence IDs 823, 829, and 851, 52) Sequence IDs 823, 829, and 852, 53) Sequence IDs 823, 829, and 853, 54) Sequence IDs 823, 829, and 854, 55) Sequence IDs 823, 829, and 855, 56) Sequence IDs 823, 829, and 856, 57) Sequence IDs 823, 829, and 857, 58) Sequence IDs 823, 829, and 858, 59) Sequence IDs 823, 829, and 859, 60) Sequence IDs 823, 829, and 860, 61) Sequence IDs 863, 862, and 861, 62) Sequence IDs 863, 864, and 861, 63) Sequence IDs 863, 864, and 865, 64) Sequence IDs 863, 866, and 865, 65) Sequence numbers 863, 868, and 867, 66) Sequence I...

Claims

[Claim 1] The invention described in the specification.

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