MULTISPECIFIC ANTIBODIES TARGETING MULTIPLE EPITOPES ON THE HIV-1 ENVELOPE

1 . One or more vectors comprising a nucleic acid encoding a multispecific anti-HIV antibody that binds to multiple epitopes on HIV envelope protein, wherein the antibody comprises:

i. an amino acid sequence that binds to a V1/V2 apex glycan epitope;

ii. an amino acid sequence that binds to a V3-base glycan region epitope;

iii. an amino acid sequence that binds to a CD4 binding site (CD4bs) epitope;

iv. an amino acid sequence that binds to a gp120/gp41 interface epitope; and

v. an amino acid sequence that binds to a membrane proximal external region (MPER) epitope.

2 . The one or more vectors of claim 1 , wherein the multispecific anti-HIV antibody that binds to multiple epitopes on HIV envelope protein, comprises

i. amino acid sequences that bind to a V1/V2 apex glycan epitope selected from the group consisting of:

a) an amino acid sequence comprising a CDR H1, CDR H2 and CDR H3, wherein CDR H1 comprises QFRFDGYG (SEQ ID NO: 2), CDR H2 comprises ISHDGIKK (SEQ ID NO: 3) and CDR H3 comprises AKDLREDECEEWWSDDFGKQLPCAKSRGGLVGIADN (SEQ ID NO: 4); and an amino acid sequence comprising a CDR L1, CDR L2 and CDR L3, wherein CDR L1 comprises TSNIGNNF (SEQ ID NO: 6), CDR L2 comprises ETD (SEQ ID NO:7) and CDR L3 comprises ATWAASLSSARV (SEQ ID NO: 8); and

b) an amino acid sequence comprising a CDR H1, CDR H2 and CDR H3, wherein CDR H1 comprises GNTLKTYD SEQ ID NO: 10), CDR H2 comprises ISHEGDKK (SEQ ID NO: 11) and CDR H3 comprises AKGSKHRLRDYALDDDGALNWAVDVDYLSNLEF (SEQ ID NO: 12); and an amino acid sequence comprising a CDR L1, CDR L2 and CDR L3, wherein CDR L1 comprises HSLIHGDRNNY (SEQ ID NO: 14), CDR L2 comprises LAS (SEQ ID NO: 15) and CDR L3 comprises MQGRESPWT (SEQ ID NO: 16);

ii. an amino acid sequence that binds to a V3-base glycan region epitope, wherein the amino acid comprises a CDR H1, CDR H2 and CDR H3, wherein CDR H1 comprises GASISDSY (SEQ ID NO: 18), CDR H2 comprises VHKSGDT (SEQ ID NO:19) and CDR H3 comprises ARTLHGRRIYGIVAFNEWFTYFYMDV (SEQ ID NO: 20); and an amino acid sequence comprising a CDR L1, CDR L2 and CDR L3, wherein CDR L1 comprises SLGSRA (SEQ ID NO: 22), CDR L2 comprises NNQ (SEQ ID NO: 23) and CDR L3 comprises HIWDSRVPTKWV (SEQ ID NO: 24);

iii. an amino acid sequence that binds to a CD4 binding site (CD4bs) epitope wherein the amino acid comprises a CDR H1, CDR H2 and CDR H3, wherein CDR H1 comprises GYTFTAHI (SEQ ID NO: 26), CDR H2 comprises IKPQYGAV (SEQ ID NO: 27) and CDR H3 comprises AR (SEQ ID NO: 28); and an amino acid sequence comprising a CDR L1, CDR L2 and CDR L3, wherein CDR L1 comprises QGVGSD (SEQ ID NO: 30, CDR L2 comprises HTS (SEQ ID NO: 31) and CDR L3 comprises QVLQF (SEQ ID NO: 32);

iv. an amino acid sequence that binds to a gp120/gp41 interface epitope wherein the amino acid sequence comprises a CDR H1, CDR H2 and CDR H3, wherein CDR H1 comprises GYRFNFYH (SEQ ID NO: 34), CDR H2 comprises ISPYSGDK (SEQ ID NO: 35) and CDR H3 comprises DDTGTYFCAKGLLRDGSSTWLPYL (SEQ ID NO: 36); and an amino acid sequence comprising a CDR L1, CDR L2 and CDR L3, wherein CDR L1 comprises NSVCCSHKS (SEQ ID NO: 38), CDR L2 comprises EDN (SEQ ID NO: 39) and CDR L3 comprises CSYTHNSGCV (SEQ ID NO: 40); and

v. an amino acid sequence that binds to a membrane proximal external region (MPER) epitope wherein the amino acid sequence comprises a CDR H1, CDR H2 and CDR H3, wherein CDR H1 comprises GFDFDNAW (SEQ ID NO: 42, CDR H2 comprises ITGPGEGWSV (SEQ ID NO: 43) and CDR H3 comprises TGYYFCARTGKYYDFWSGYPPGEEYFQD (SEQ ID NO: 44); and an amino acid sequence comprising a CDR L1, CDR L2 and CDR L3, wherein CDR L1 comprises RGDSLRSHYAS (SEQ ID NO: 46), CDR L2 comprises GKNNRPS (SEQ ID NO: 47) and CDR L3 comprises SSRDKSGSRLSV (SEQ ID NO: 48).

3 . The one or more vectors of claim 1 , wherein the antibody simultaneously binds the multiple epitopes.

4 . The one or more vectors of claim 1 , wherein the amino acid sequences of i-v) are present on a single polypeptide chain.

5 . The one or more vectors of claim 1 , wherein the antibody is capable of neutralizing at least 99% of the HIV viruses or HIV pseudoviruses listed in Table 1 with an IC50 value of less than 50 μg/mL.

6 . The one or more vectors of claim 2 , wherein the antibody simultaneously binds the multiple epitopes.

7 . The one or more vectors of claim 2 , wherein the amino acid sequences of i-v) are present on a single polypeptide chain.

8 . The one or more vectors of claim 2 , wherein the antibody is capable of neutralizing at least 99% of the HIV viruses or HIV pseudoviruses listed in Table 1 with an IC50 value of less than 50 μg/mL.

9 . The one or more vectors of claim 1 , wherein the vector is a viral vector.

10 . The one or more vector of claim 2 , wherein the vector is a viral vector.

11 . A cell, or engineered cell, comprising the one or more vectors of claim 1 .

12 . A cell, or engineered cell, comprising the one or more vectors of claim 2 .

13 . The cell, or engineered cell of claim 11 , wherein the cell is an immune cell.

14 . The cell, or engineered cell, of claim 13 , wherein the immune cell is a B cell.

15 . The cell, or engineered cell of claim 12 , wherein the cell is an immune cell.

16 . The cell of claim 15 , wherein the immune cell is a B cell.

17 . A pharmaceutical composition comprising the cell of claim 11 , and a pharmaceutically acceptable carrier.

18 . A pharmaceutical composition comprising the cell of claim 12 , and a pharmaceutically acceptable carrier.

19 . A method for treating or preventing HIV infection in a subject, comprising administering to the subject an effective amount of the composition of claim 16 .

20 . The method of claim 19 , wherein the composition is administered in combination with another therapy, and optionally, wherein the therapy is an anti-retroviral therapy.