Truncated HIV envelope proteins (ENV), methods and compositions related thereto
The instant application provides methods and related compositions pertaining to novel HIV envelope proteins. In some embodiments, the invention relates to methods and compositions for the preparation, production, and administration of isolated novel HIV envelope nucleic acid and protein sequences suitable, for example, as vaccines against HIV.
1. An isolated peptide comprising a truncated HIV Env protein, wherein the HIV Env protein:
(i) is mutated in the native gp120/gp41 cleavage site to prevent protease cleavage,
(ii) comprises the NITER of gp41,
(iii) is truncated prior to the transmembrane domain; and
(iv) comprises about 1-10 hydrophilic amino acids at its C-terminus; and
wherein the peptide comprises an amino acid sequence having 99% or greater identity to the amino acid sequence depicted in SEQ ID NO: 1.
2. The peptide of claim 1 , wherein the about 1-10 hydrophilic amino acids are three lysines.
3. The peptide of claim 1 , wherein the MPER of gp41 comprises the 4E10 epitope.
4. The peptide of claim 3 , wherein the MPER of gp41 comprises the amino acid sequence: L WYIK (SEQ ID NO: 24) at its C-terminus.
5. The peptide of claim 4 , wherein the HIV Env protein comprises about 1-10 non-native hydrophilic amino acids C-terminal to and contiguous with the L WYIK (SEQ ID NO: 24) amino acid sequence.
6. The peptide of claim 1 , wherein the peptide comprises the amino acid sequence depicted in SEQ ID NO: 1.
7. A composition comprising the peptide of claim 1 and a pharmaceutically acceptable carrier.
8. A method of generating antibodies against HIV in a mammal, comprising administering the composition of claim 7 to the mammal.
9. The method of claim 8 , wherein the composition further comprises an adjuvant.
10. A method of conferring immunity against HIV in a mammal, comprising administering the composition of claim 7 to the mammal.
11. The method of claim 10 , wherein the composition further comprises an adjuvant.
12. The method of claim 10 , comprising administering the composition to the mammal by injection.
13. The method of claim 10 , wherein the mammal is selected from the group consisting of: a human, a non-human primate, a dog, a rabbit, a guinea pig, and a mouse.
14. A subunit vaccine comprising the peptide of claim 1 .
15. An isolated peptide comprising an amino acid sequence having 99% or greater identity to a-14 the amino acid sequence depicted in SEQ ID NO:3.
16. An isolated peptide comprising the amino acid sequence depicted in SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:5.
17. A kit comprising (a) the composition of claim 7 and (b) instructions for administration of the composition to a mammal.
18. An isolated peptide comprising an amino acid sequence having 98% or greater identity to the amino acid sequence depicted in SEQ ID NO:7 or SEQ ID NO:9.
19. The peptide of claim 18 , wherein the peptide comprises an amino acid sequence having 99% or greater identity to an amino acid sequence depicted in SEQ ID NO: 7 or SEQ ID NO: 9.
20. The peptide of claim 19 , wherein the peptide comprises the amino acid sequence depicted in SEQ ID NO: 7 or SEQ ID NO: 9.
21. The method of claim 11 , wherein the adjuvant comprises a liposome formulation.
22. The method of claim 21 , wherein the liposome formulation comprises one or more of: dimyristoyl phosphatidylcholine, dimyristoyl phosphatidylglycerol, cholesterol, and phospholipid.
23. The method of claim 22 , wherein the liposome formulation comprises phospholipid A.
24. The method of claim 8 , wherein the antibodies generated in the mammal are antibodies that compete with the peptide comprising the truncated HIV Env protein for binding integrin α4β7.
25. The isolated peptide of claim 1 , wherein the peptide binds integrin α4β7.