Broadly neutralizing antibody and uses thereof
The present invention relates to an exceptionally broad and potent neutralizing antibody which may comprise cross-clade neutralizing coverage of 83% at a median IC 50 of 0.003 μg/ml, compositions containing the same and uses thereof.
1. A non-naturally occurring anti-HIV-1 monoclonal antibody or antigen binding portion thereof, comprising (a) a heavy chain sequence comprising an amino acid sequence encoded by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13 and (b) a light chain sequence comprising an amino acid sequence encoded by SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26.
2. The non-naturally occurring anti-HIV-1 monoclonal antibody of claim 1 , wherein the heavy chain sequence is encoded by SEQ ID NO: 1 and the light chain sequence is encoded by SEQ ID NO: 14.
3. A composition comprising the antibody of claim 1 .
4. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
5. The antibody or antigen binding portion of claim 1 , wherein the heavy chain sequence comprises a third complementarity determining region (CDRE3) of 33 to 34 amino acid residues.
6. The antibody or antigen binding portion of claim 5 , wherein a triad of aspartic acid residues at the tip of CDRH3 provides an anionic potential to the CDRH3.
7. An isolated polypeptide comprising an antigen-binding antibody fragment of an anti-HIV-1 antibody, wherein the antibody fragment comprises
(a) the heavy chain CDRs of a heavy chain sequence encoded by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13, and
(b) the light chain CDRs of a light chain sequence encoded by SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26,
wherein the isolated polypeptide is not an intact antibody.
8. The isolated polypeptide of claim 7 , wherein the antibody fragment comprises the heavy chain CDR3 of any one of SEQ ID NO: 40-52 and the light chain CDR3 of any one of SEQ ID NO: 58-70.
9. The isolated polypeptide of claim 7 , wherein the antibody fragment comprises the heavy chain CDR3 of SEQ ID NO: 40, and the light chain CDR3 of SEQ ID NO: 58.
10. The isolated polypeptide of claim 8 , wherein a triad of aspartic acid residues at the tip of heavy chain CDR3 provides an anionic potential to the heavy chain CDR3.
11. The isolated polypeptide of claim 7 , wherein the antibody fragment comprises
(a) a heavy chain variable region comprising an amino acid sequence encoded by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13 and
(b) a light chain variable region comprising an amino acid sequence encoded by SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, or SEQ ID NO: 26.
12. The isolated polypeptide of claim 11 , wherein the heavy chain sequence is encoded by SEQ ID NO: 1 and the light chain sequence is encoded by SEQ ID NO: 14.
13. The isolated polypeptide of claim 7 , wherein the antibody fragment comprises
(a) a heavy chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 1, and
(b) a light chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 14.
14. The isolated polypeptide of claim 13 , wherein the antibody fragment comprises the heavy chain CDR3 of SEQ ID NO: 40, and the light chain CDR3 of SEQ ID NO: 58.
15. The isolated polypeptide of claim 13 , wherein the heavy chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 1, and the light chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 14.
16. An isolated polypeptide comprising an antigen-binding antibody fragment of an anti-HIV-1 antibody, wherein the antibody fragment comprises
(a) a heavy chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 1, and
(b) a light chain variable region comprising an amino acid sequence with at least 90% identity to the amino acid sequence encoded by SEQ ID NO: 14,
wherein the isolated polypeptide interacts with HIV gp120 V1/V2 domain of BG505, and
wherein the isolated polypeptide is not an intact antibody.
17. The isolated polypeptide of claim 16 , wherein the heavy chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 1, and the light chain variable region comprises an amino acid sequence with at least 95% identity to the amino acid sequence encoded by SEQ ID NO: 14.
18. The isolated polypeptide of claim 16 , wherein the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 40, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 58.
19. A pharmaceutical composition comprising the isolated polypeptide of claim 7 and a pharmaceutically acceptable carrier.
20. A pharmaceutical composition comprising the isolated polypeptide of claim 8 and a pharmaceutically acceptable carrier.
21. A pharmaceutical composition comprising the isolated polypeptide of claim 9 and a pharmaceutically acceptable carrier.
22. A pharmaceutical composition comprising the isolated polypeptide of claim 10 and a pharmaceutically acceptable carrier.
23. A pharmaceutical composition comprising the isolated polypeptide of claim 11 and a pharmaceutically acceptable carrier.
24. A pharmaceutical composition comprising the isolated polypeptide of claim 12 and a pharmaceutically acceptable carrier.
25. A pharmaceutical composition comprising the isolated polypeptide of claim 13 and a pharmaceutically acceptable carrier.
26. A pharmaceutical composition comprising the isolated polypeptide of claim 14 and a pharmaceutically acceptable carrier.
27. A pharmaceutical composition comprising the isolated polypeptide of claim 15 and a pharmaceutically acceptable carrier.
28. A pharmaceutical composition comprising the isolated polypeptide of claim 16 and a pharmaceutically acceptable carrier.
29. A pharmaceutical composition comprising the isolated polypeptide of claim 17 and a pharmaceutically acceptable carrier.
30. A pharmaceutical composition comprising the isolated polypeptide of claim 18 and a pharmaceutically acceptable carrier.