HIV-1 envelope protein associated with a broadly reactive neutralizing antibody response
View Patent ↗The present invention relates to HIV-1 envelope proteins from a donor with non-progressive HIV-1 infection whose serum contains broadly cross-reactive, primary virus neutralizing antibody. The invention also relates to isolated or purified proteins and protein fragments that share certain amino acids at particular positions with the foregoing HIV-1 proteins.
1. An isolated HIV envelope protein capable of inducing the production of a cross-reactive neutralizing anti-serum against multiple strains of HIV-1 in vitro comprising an amino acid sequence with at least ninety-two (92) percent sequence identity to SEQ ID NO: 1.
2. The isolated HIV envelope protein of claim 1 wherein the protein comprises an amino acid sequence with at least ninety-five (95) percent sequence identity to SEQ ID NO: 1.
3. The isolated HIV envelope protein of claim 1 wherein the protein comprises an amino acid sequence with at least ninety-eight (98) percent sequence identity to SEQ ID NO: 1.
4. The isolated HIV envelope protein of claim 1 wherein the protein comprises an amino acid sequence with at least ninety-nine (99) percent sequence identity to SEQ ID NO: 1.
5. An isolated HIV envelope protein capable of inducing the production of a cross-reactive neutralizing anti-serum against multiple strains of HIV-1 in vitro wherein the V3 region of the HIV envelope protein comprises amino acids 13 to 25 of SEQ ID NO: 3.
6. The isolated HIV envelope protein of claim 5 wherein the protein comprises an amino acid sequence with at least ninety (90) percent sequence identity in the V3 region of SEQ ID NO: 1.
7. The isolated HIV envelope protein of claim 5 wherein the protein comprises an amino acid sequence with at least ninety-five (95) percent sequence identity in the V3 region of SEQ ID NO: 1.
8. The isolated HIV envelope protein of claim 5 wherein the protein comprises an amino acid sequence with at least ninety-nine (99) percent sequence identity in the V3 region of SEQ ID NO: 1.
9. The isolated HIV envelope protein of claim 5 wherein the V3 region comprises the amino acid sequence of SEQ ID NO: 3.
10. The isolated HIV envelope protein of claim 1 or 5 wherein the protein comprises a cyclic peptide.
11. The isolated HIV envelope protein of claim 1 or 5 wherein the protein is at least 95 amino acid residues in length.
12. The isolated HIV envelope protein of claim 1 or 5 wherein the HIV envelope protein is recombinantly produced.
13. The isolated HIV envelope protein of claim 1 or 5 wherein the protein is glycosylated at one or more amino acid residues.
14. The isolated HIV envelope protein of claim 1 or 5 wherein the HIV envelope protein is synthetically produced.
15. The isolated HIV envelope protein of claim 1 or 5 wherein the protein is linked to a second protein.
16. The isolated HIV envelope protein of claim 15 wherein the protein is linked to the second protein by a peptide linker.
17. An isolated HIV envelope protein comprising the amino acid sequence of SEQ ID NO: 1.
18. An isolated HIV envelope protein consisting of the amino acid sequence of SEQ ID NO: 1.
19. A composition comprising an isolated HIV-1 envelope protein of any one of claims 1 , 5 , 17 or 18 and a pharmaceutically acceptable carrier.
20. The composition of claim 19 further comprising an adjuvant.
21. The composition of claim 19 wherein the composition is suitable for use in humans.
22. A method of generating antibodies in a mammal comprising administering the composition of claim 19 .
23. A method of generating antibodies in a mammal comprising administering the isolated HIV-1 envelope protein of claim 1 or 5 .
24. The method of claim 23 wherein the mammal is a human.
25. The method of claim 23 wherein the antibodies produced are monoclonal.
26. The method of claim 25 wherein the mammal is a mouse.
27. The method of claim 25 further comprising humanizing the monoclonal antibody.
28. The method of claim 23 wherein the antibodies produced are polyclonal.
29. The method of claim 23 wherein the mammal is a primate.