HIV-1 neutralizing antibodies and uses thereof (CD4bs antibodies)
The invention relates to the identification of monoclonal HIV-1 neutralizing antibodies, such as, but not limited to, antibodies that bind to the CD4 binding site (CD4bs) of HIV-1 gp120, their recombinant expression and purification and uses. In certain aspects, the invention provides a pharmaceutical composition comprising anyone of the antibodies of the invention or fragments thereof or any combination thereof. In certain aspects the invention provides methods to treat or prevent HIV-1 infection in a subject comprising administering to the subject a pharmaceutical composition comprising any one of the inventive antibodies or fragments thereof.
1. An anti-HIV-1 envelope recombinant monoclonal 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 antibody CH557 (SEQ ID NO: 124) and comprises a VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of antibody CH557 (SEQ ID NO: 125).
2. An anti-HIV-1 envelope recombinant monoclonal antibody or antigen-binding fragment thereof wherein the antibody or antigen-binding fragment thereof comprises the VH chain of antibody CH557 (SEQ ID NO: 124) and the VL chain of antibody CH557 (SEQ ID NO: 125).
3. The anti-HIV-1 envelope recombinant monoclonal antibody or antigen-binding fragment thereof of claim 1 wherein the antibody or fragment thereof comprises a modified Fc portion.
4. The anti-HIV-1 envelope recombinant monoclonal antibody or antigen-binding fragment thereof of claim 1 wherein the antibody or antigen-binding fragment thereof is bispecific.
5. A pharmaceutical composition comprising any one of the antibodies or antigen-binding fragments thereof of claim 1 .
6. A composition comprising a vector comprising a nucleic acid encoding the anti-HIV-1 envelope antibody or antigen-binding fragment thereof of claim 1 .
7. The composition of claim 6 , wherein the vector is suitable for gene delivery and expression.
8. A method to treat HIV-1 infection in a subject comprising administering to the subject a composition comprising an anti-HIV-1 envelope recombinant monoclonal 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 antibody CH557 (SEQ ID NO: 124) and comprises a VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of antibody CH557 (SEQ ID NO: 125) in a therapeutically effective amount.
9. The method of claim 8 further comprising administering an additional HIV-1 broad neutralizing antibody.
10. The method of claim 8 , wherein the antibody or antigen-binding fragment thereof is administered as a nucleic acid.
11. The method of claim 8 , wherein the antibody or antigen-binding fragment thereof comprises a modified Fc portion.
12. The antibody or antigen-binding fragment thereof of claim 2 wherein the antibody or antigen-binding fragment thereof comprises a modified Fc portion.
13. The antibody or antigen-binding fragment thereof of claim 2 wherein the antibody or antigen-binding fragment thereof is bispecific.
14. A pharmaceutical composition comprising any one of the antibodies or antigen-binding fragments thereof of claim 2 .
15. A pharmaceutical composition comprising any one of the antibodies or antigen-binding fragments thereof of claim 12 .
16. A pharmaceutical composition comprising any one of the antibodies or antigen-binding fragments thereof of claim 13 .
17. A pharmaceutical composition comprising any one of the antibodies or antigen-binding fragments thereof of claim 3 .
18. A pharmaceutical composition comprising any one of the antibodies or antigen-binding fragments thereof of claim 4 .
19. A composition comprising a vector comprising a nucleic acid encoding the antibody or antigen-binding fragment thereof of any one of claim 2 .
20. The composition of claim 19 , wherein the vector is suitable for gene delivery and expression.
21. An anti-HIV-1 envelope recombinant monoclonal antibody or antigen-binding fragment thereof wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising a heavy chain complementarity determining region (HCDR)1, a HCDR2, and a HCDR3 comprising amino acids 26-33, 51-58, and 96-112 of SEQ ID NO: 124, respectively; and a light chain variable region comprising a light chain complementarity determining region (LCDR)1, a LCDR2, and a LCDR3, comprising amino acids 27-32, 50-52 and 88-97 of SEQ ID NO: 125, respectively.
22. The anti-HIV-1 envelope recombinant monoclonal antibody or antigen-binding fragment thereof of claim 21 wherein the antibody or fragment thereof comprises a modified Fc portion.
23. The anti-HIV-1 envelope recombinant monoclonal antibody or antigen-binding fragment thereof of claim 21 wherein the antibody or antigen-binding fragment thereof is bispecific.
24. A pharmaceutical composition comprising any one of the antibodies or antigen-binding fragments thereof of claim 21 .
25. A composition comprising a vector comprising a nucleic acid encoding the anti-HIV-1 envelope antibody or antigen-binding fragment thereof of claim 21 .
26. The composition of claim 25 , wherein the vector is suitable for gene delivery and expression.
27. A method to treat HIV-1 infection in a subject comprising administering to the subject in a therapeutically effective amount a composition comprising an anti-HIV-1 envelope recombinant monoclonal antibody or antigen-binding fragment thereof wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising a heavy chain complementarity determining region (HCDR)1, a HCDR2, and a HCDR3 comprising amino acids 26-33, 51-58, and 96-112 of SEQ ID NO: 124, respectively; and a light chain variable region comprising a light chain complementarity determining region (LCDR)1, a LCDR2, and a LCDR3, comprising amino acids 27-32, 50-52 and 88-97 of SEQ ID NO: 125, respectively.
28. The method of claim 27 further comprising administering an additional HIV-1 broad neutralizing antibody.
29. The method of claim 27 , wherein the antibody or antigen-binding fragment thereof is administered as a nucleic acid.
30. The method of claim 27 , wherein the antibody or antigen-binding fragment thereof comprises a modified Fc portion.
31. An anti-HIV-1envelope recombinant monoclonal 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 antibody CH557 (SEQ ID NO: 124) and comprises a VL chain that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the VL chain of antibody CH557 (SEQ ID NO: 125) produced by a process comprising transfecting a mammalian host cell with one or more vectors comprising a nucleic acid encoding the anti-HIV-1 envelope antibody or antigen-binding fragment thereof and culturing the transfected mammalian host cells.
32. The anti-HIV-1 envelope recombinant monoclonal antibody or antigen-binding fragment thereof of claim 31 , wherein the antibody or antigen-binding fragment thereof comprises the VH chain of antibody CH557 (SEQ ID NO: 124) and the VL chain of antibody CH557 (SEQ ID NO: 125).
33. The anti-HIV-1 envelope recombinant monoclonal antibody or antigen-binding fragment thereof of claim 31 , wherein the antibody or fragment thereof comprises a modified Fc portion.
34. The anti-HIV-1 envelope recombinant monoclonal antibody or antigen-binding fragment thereof of claim 31 , wherein the antibody or antigen-binding fragment thereof is bispecific.
35. A pharmaceutical composition comprising any one of the antibodies or antigen-binding fragments thereof of claim 31 .
36. An anti-HIV-1 envelope recombinant monoclonal antibody or antigen-binding fragment thereof wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising a heavy chain complementarity determining region (HCDR)1, a HCDR2, and a HCDR3 comprising amino acids 26-33, 51-58, and 96-112 of SEQ ID NO: 124, respectively; and a light chain variable region comprising a light chain complementarity determining region (LCDR)1, a LCDR2, and a LCDR3, comprising amino acids 27-32, 50-52 and 88-97 of SEQ ID NO: 125, respectively produced by a process comprising transfecting a mammalian host cell with one or more vectors comprising a nucleic acid encoding the anti-HIV-1 envelope antibody or antigen-binding fragment thereof and culturing the transfected mammalian host cells.
37. The anti-HIV-1 envelope recombinant monoclonal antibody or antigen-binding fragment thereof of claim 36 , wherein the antibody or fragment thereof comprises a modified Fc portion.
38. The anti-HIV-1 envelope recombinant monoclonal antibody or antigen-binding fragment thereof of claim 36 , wherein the antibody or antigen-binding fragment thereof is bispecific.
39. A pharmaceutical composition comprising any one of the antibodies or antigen-binding fragments thereof of claim 36 .