Methods for the induction of broadly anti-HIV-1 neutralizing antibody responses employing liposome-MPER peptide compositions
The present invention relates in general, to a formulation suitable for use in inducing anti-HIV-1 antibodies, and, in particular, to a formulation comprising Toll Like Receptor (TLR) agonists with HIV-1 gp41 membrane proximal external region (MPER) peptide-liposome conjugates for induction of broadly reactive anti-HIV-1 antibodies. The invention also relates to methods of inducing neutralizing anti-HIV-1 antibodies using such formulations.
1. A method of inducing the production in a subject of anti-HIV-1 antibodies comprising administering to said subject a composition comprising a liposome-peptide conjugate in an amount sufficient to effect said induction, wherein said peptide comprises SEQ ID NO:17 (NEQELLELDKWASSWNWFNITNWLWYIK) presented on the surface of said liposome.
2. The method according to claim 1 wherein said peptide further comprises a hydrophobic linker.
3. The method according to claim 2 wherein said linker is C-terminal to said MPER epitope.
4. The method according to claim 2 wherein said linker is GTH1.
5. The method according to claim 1 wherein said peptide is NEQELLELDKWASSWNWFNITNWLWYIK (SEQ ID NO: 17) presented on the surface of the liposome via the GTH1 linker.
6. The method according to claim 1 wherein the composition further comprises an adjuvant.
7. The method according to claim 6 wherein said adjuvant is a Toll Like Receptor (TLR) ligand.
8. The method according to claim 7 wherein said TLR ligand is a TLR9 ligand.
9. The method according to claim 8 wherein said TLR9 ligand is oligo CpG.
10. The method according to claim 7 wherein said TLR ligand is a TLR7/8 ligand.
11. The method according to claim 10 wherein said TLR7/8 ligand is R-848.
12. The method according to claim 7 wherein said TLR ligand is a TLR4 ligand.
13. The method according to claim 12 wherein said TLR4 ligand is monophosphorylipid A.
14. The method according to claim 7 wherein said conjugate comprises a TLR9 ligand and a TLR7/8 ligand.
15. The method according to claim 14 wherein said TLR9 ligand is oligo CpG and said TLR7/8 ligand is R-848.
16. The method according to claim 7 wherein said conjugate comprises a TLR9 ligand and a TLR4 ligand.
17. The method according to claim 16 wherein said TLR9 ligand is oligo CpG and said TLR4 ligand is R-848.
18. The method according to claim 7 wherein said composition further comprises interferon-αencapsulated therewithin.
19. The method according to claim 7 wherein said composition is administered as a prime or a boost.
20. A composition comprising a liposome and an MPER peptide comprising the peptide of SEQ ID NO:17, wherein the peptide is presented on the surface of the liposome via a hydrophobic linker.
21. The composition according to claim 20 further comprising interferon-α encapsulated within said liposome.
22. The composition of claim 20 further comprising an adjuvant.
23. The composition of claim 21 , wherein the adjuvant is a Toll Like Receptor (TLR) ligand.
24. The composition of claim 21 , wherein the TLR ligand is TLR4, TLR7/8, TLR9, or any combination thereof.
25. The composition of claim 24 , wherein the TLR4 ligand is monophosphorylipid A.
26. The composition of claim 24 , wherein the TLR7/8 ligand is R848.
27. The composition of claim 24 , wherein the TLR9 ligand is oligoCpG.
28. The composition of claim 24 , wherein the linker is GTH1.