HIV-1 neutralizing antibodies and uses thereof (V3 antibodies)
The invention is directed to HIV-1 neutralizing antibodies, CD4 binding site and V3 glycan antibodies, and methods for their uses.
1. An anti-HIV-1 recombinant antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises:
a VH chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VH chain of SEQ ID NO: 3 and
a VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of SEQ ID NO: 4 or a VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of SEQ ID NO: 155, or
a VL chain that is 90%, 91%, 92%, 93%, 94, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of SEQ ID NO: 116.
2. An anti-HIV-1 recombinant antibody or an antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises:
a VH chain of SEQ ID NO: 3, 17, 19, 20, 21, 26, 27, 28, 162, 163, 164, 165 or 166 and
a VL chain of SEQ ID NO: 41, 44, 45, 48, 50, 51, 52, 116 or 149.
3. The anti-HIV-1 recombinant antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises:
a VH chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,98%, 99% or 100% identical to the VH chain of SEQ ID NO: 3 and
a VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of SEQ ID NO: 4.
4. The anti-HIV-1 recombinant antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises:
a VH chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VH chain of SEQ ID NO: 3 and
a VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of SEQ ID NO: 155.
5. The anti-HIV-1 recombinant antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises:
a VH chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VH chain of SEQ ID NO: 3 and
a VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of SEQ ID NO: 116.
6. The anti-HIV-1 recombinant antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or fragment thereof comprises:
a VH chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VH chain of SEQ ID NO:3 and the VL chain of SEQ ID NO: 4, the VL chain of SEQ ID NO: 116 or the VL chain of SEQ ID NO: 155.
7. The anti-HIV-1 recombinant antibody or antigen-binding fragment thereof of claim 1 comprising the VH chain of SEQ ID NO: 3 and the VL chain of SEQ ID NO: 4.
8. The anti-HIV-1 recombinant antibody or antigen-binding fragment thereof of claim 1 comprising the VH chain of SEQ ID NO: 3 and the VL chain of SEQ ID NO: 116.
9. The anti-HIV-1 recombinant antibody or antigen-binding fragment thereof of claim 1 comprising the VH chain of SEQ ID NO: 3 and the VL chain of SEQ ID NO:155.
10. The anti-HIV-1 recombinant antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a modified Fc portion.
11. The anti-HIV-1 recombinant antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is bispecific.
12. A pharmaceutical composition comprising any one of the antibodies or antigen-binding fragments thereof of claim 1 .
13. A pharmaceutical composition comprising any one of the antibodies or antigen-binding fragments thereof of claim 1 and another HIV-1 broadly neutralizing antibody.
14. A composition comprising a vector comprising a nucleic acid encoding the antibody or antigen-binding fragment thereof of claim 1 .
15. The composition of claim 14 , wherein the vector is suitable for gene delivery and expression.
16. A method to treat HIV-1 infection in a subject comprising administering to the subject a composition comprising an anti-HIV-1 recombinant antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises:
a VH chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VH chain of SEQ ID NO: 3 and
a VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100identical to the VL chain of SEQ ID NO: 4 or a VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of SEQ ID NO:155 or
a VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of SEQ ID NO: 116 in a therapeutically effective amount.
17. The method of claim 16 wherein the pharmaceutical composition is administered in a therapeutically effective dose and regimen.
18. The method of claim 16 further comprising administering an additional HIV-1 broadly neutralizing antibody.
19. The method of claim 16 , wherein the antibody or antigen-binding fragment is administered as a nucleic acid.
20. The method of claim 16 , wherein the antibody or antigen-binding fragment comprises a modified Fc portion.
21. A method to treat HIV-1 infection in a subject comprising administering to the subject a composition comprising the anti-HIV-1 recombinant antibody or antigen-binding fragment thereof of claim 7 in a therapeutically effective amount.
22. A method to treat HIV-1 infection in a subject comprising administering to the subject a composition comprising the recombinant antibody or antigen-binding fragment thereof of claim 8 in a therapeutically effective amount.
23. A method to treat HIV-1 infection in a subject comprising administering to the subject a composition comprising the recombinant antibody or antigen-binding fragment thereof of claim 9 in a therapeutically effective amount.
24. The anti-HIV-1 envelope recombinant antibody or antigen-binding fragment thereof of claim 2 , wherein the VL chain comprises an amino acid sequence of SEQ ID NO: 4, 147, 150, 151, 154, 155, or 156.