Synthetic hapten carrier compositions and methods
The present disclosure relates to peptide monomers comprising an amphipathic ?-helical peptide, and optionally, at least one T cell epitope peptide; and to dimers and trimers comprising the peptide monomers. The monomeric, dimeric, and trimeric peptides may be conjugated to at least one hapten, wherein the hapten is linked to a lysine or aspartic acid residue of the peptide monomer. These peptide conjugates are useful as vaccine delivery vehicles.
1. A peptide monomer comprising an amphipathic α-helical peptide comprising an amino acid sequence with at least 80% identity to SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:3.
2. The peptide monomer of claim 1 , wherein the amphipathic α-helical peptide comprises an amino acid sequence with at least 90% identity to SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:3.
3. The peptide monomer of claim 1 , wherein the amphipathic α-helical peptide comprises an amino acid sequence with 100% identity to SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:3.
4. The peptide monomer of claim 1 , further comprising at least one T cell epitope peptide linked to the C-terminus of the amphipathic α-helical peptide.
5. The peptide monomer according to claim 1 , wherein the amphipathic α-helical peptide comprises an amino acid sequence according to the formula: (E or X)XIEXR-[I(E or X)XIEXR] n -I(E or X)X,
wherein X=K for each instance; or each X is independently selected from D and E; and n=3, 4, 5, 6, 7, 8, 9, or 10.
6. The peptide monomer according to claim 4 , wherein the amphipathic α-helical peptide comprises an amino acid sequence according to the formula: (E or X)XIEXR-[I(E or X)XIEXR] n -I(E or X)X,
wherein X=K for each instance; or each X is independently selected from D and E; and n=3, 4, 5, 6, 7, 8, 9, or 10.
7. The peptide monomer according to claim 4 , wherein the at least one T cell epitope peptide is a CD4 + T cell epitope peptide.
8. The peptide monomer of claim 4 , wherein the CD4 + T cell epitope peptide is a promiscuous CD4 + T cell epitope peptide or comprises the amino acid sequence set forth in SEQ ID NO:10.
9. The peptide monomer of claim 4 , wherein the at least one T cell epitope peptide is a T cell epitope peptide of a pathogenic microorganism or is an influenza hemagglutinin T cell epitope peptide.
10. The peptide monomer of claim 9 , wherein the at least one T cell epitope peptide comprises the amino acid sequence set forth in SEQ ID NO:6.
11. The peptide monomer of claim 4 , wherein at least two T cell epitope peptides are fused in series to the C-terminus of the amphipathic α-helical peptide.
12. A peptide dimer comprising a peptide monomer according to claim 1 , wherein the peptide dimer is configured in a coiled-coil, comprising a parallel bundle of the two peptide monomers.
13. A peptide dimer comprising a peptide monomer according to claim 4 , wherein the peptide dimer is configured in a coiled-coil, comprising a parallel bundle of the two peptide monomers.
14. A trimeric peptide comprising a peptide monomer according to claim 1 , wherein the trimeric peptide is configured in a coiled-coil, comprising a parallel bundle of the three peptide monomers.
15. A trimeric peptide comprising a peptide monomer according to claim 4 , wherein the trimeric peptide is configured in a coiled-coil, comprising a parallel bundle of the three peptide monomers.
16. A peptide carrier conjugate comprising the trimeric coiled-coil peptide of claim 14 linked to at least one hapten, wherein the at least one hapten is linked to a lysine or aspartic acid or glutamic acid residue of at least one peptide monomer of said three peptide monomers of which the trimeric coiled-coil peptide is comprised.
17. A peptide carrier conjugate comprising the trimeric coiled-coil peptide of claim 15 linked to at least one hapten, wherein the at least one hapten is linked to a lysine or aspartic acid or glutamic acid residue of at least one peptide monomer of said three peptide monomers of which the trimeric coiled-coil peptide is comprised.
18. The peptide carrier conjugate of claim 16 , wherein the hapten is a drug of abuse.
19. The peptide carrier conjugate of claim 17 , wherein the hapten is a drug of abuse.
20. The peptide carrier conjugate of claim 18 , wherein the drug of abuse is nicotine, cocaine, methamphetamine, morphine, a cannabinoid, or an analog thereof.
21. The peptide carrier conjugate of claim 19 , wherein the drug of abuse is nicotine, cocaine, methamphetamine, morphine, a cannabinoid, or an analog thereof.
22. The peptide carrier conjugate of claim 20 , wherein the nicotine analog is nicotine 6-hexanoic acid.
23. The peptide carrier conjugate of claim 21 , wherein the nicotine analog is nicotine 6-hexanoic acid.
24. The peptide carrier conjugate of claim 16 , wherein the peptide carrier conjugate is linked to at least two haptens.
25. The peptide carrier conjugate of claim 17 , wherein the peptide carrier conjugate is linked to at least two haptens.
26. The peptide carrier conjugate of claim 24 , wherein the at least two haptens are selected from nicotine, nicotine analogs, and structurally distinct nicotine haptens.
27. The peptide carrier conjugate of claim 25 , wherein the at least two haptens are selected from nicotine, nicotine analogs, and structurally distinct nicotine haptens.
28. An immunogenic composition comprising the peptide carrier conjugate of claim 16 ; and a pharmaceutically acceptable carrier, wherein the composition is capable of inducing an immune response specific for the hapten.
29. An immunogenic composition comprising the peptide carrier conjugate of claim 17 ; and a pharmaceutically acceptable carrier, wherein the composition is capable of inducing an immune response specific for the hapten.
30. The immunogenic composition of claim 28 , wherein the immunogenic composition further comprises at least one T cell epitope peptide.
31. The immunogenic composition according to claim 28 , further comprising a pharmaceutically acceptable adjuvant.
32. The immunogenic composition according to claim 29 , further comprising a pharmaceutically acceptable adjuvant.
33. The immunogenic composition of claim 31 , wherein the adjuvant is a toll-like receptor (TLR) agonist.
34. The immunogenic composition of claim 32 , wherein the adjuvant is a toll-like receptor (TLR) agonist.
35. A method of inducing an immune response specific for a hapten in a subject, the method comprising administering to the subject the immunogenic composition according to claim 28 .
36. A method of inducing an immune response specific for a hapten in a subject, the method comprising administering to the subject the immunogenic composition according to claim 29 .