Compositions and methods for preventing and treating rhinovirus infections
An analysis of human CD4 + T-cell epitopes of RV capsid proteins with cross-reactive potential was performed, peptide epitopes of RV-A16 capsid proteins VP1 and VP2 were identified, RV-specific CD4 + T cells were phenotyped for surface markers and cytokine profiles using flow cytometry, and it was found that, among non-infected subjects, circulating RV-A16-specific CD4 + T cells detected at the highest frequencies targeted 10 unique epitopes with diverse HLA-DR binding capacity. T-cell epitopes localized to conserved regions of significance to the virus and were enriched for HLA class I and II binding motifs and were activated in vivo after experimental infection with RV-A16. RV-A16 epitopes constituted species-specific and pan-species varieties, together providing ˜90% coverage of the US population. Cross-reactivity was evidenced for RV-A16 and RV-A39. High-frequency circulating RV-specific memory Th1 cells in healthy individuals preferentially target a limited set of conserved epitopes and these epitopes, separately or combined, can serve as vaccines.
1. A method for inducing an immune response against a rhinovirus (RV) or for activating antigen-experienced RV-specific CD4 + T cells in a subject, said method comprising administering to said subject a pharmaceutical composition comprising an effective amount of at least one RV peptide epitope, wherein at least one of said RV peptide epitopes is a conserved RV peptide epitope recognized by antigen-experienced RV-specific CD4 + T cells, wherein said at least one RV peptide epitope is selected from the group consisting of SEQ ID NOs:1-53, 56, and 57, and biologically active fragments and homologs of said at least one RV peptide epitope.
2. The method of claim 1 , wherein said antigen-experienced RV-specific CD4 + T cells respond to cross-reactive determinants of different RV strains.
3. The method of claim 1 , wherein at least two RV peptide epitopes are administered.
4. The method of claim 3 , wherein at least three RV peptide epitopes are administered.
5. The method of claim 4 , wherein at least five RV peptide epitopes are administered.
6. The method of claim 5 , wherein at least ten RV peptide epitopes are administered.
7. The method of claim 1 , where said SEQ ID NO is selected from the group consisting of SEQ ID NOs:1-10.
8. The method of claim 7 , wherein each of said SEQ ID NOs:1-10 is administered.
9. The method of claim 1 , wherein said composition further comprises an adjuvant.
10. The method of claim 1 , wherein said RV peptide epitope is pan-specific.
11. The method of claim 1 , wherein when at least two RV peptide epitopes are administered, at least one of said at least two RV peptide epitopes is an RV-A16 VP1 epitope .
12. The method of claim 1 , wherein said antigen-experienced RV-specific CD4 + T cells are cross-reactive with epitopes from different RV strains.
13. The method of claim 1 , wherein said antigen-experienced RV-specific CD4 + T cells target a limited set of conserved RV peptide epitopes.
14. The method of claim 1 , wherein said antigen-experienced RV-specific CD4 + T cells recognize a limited set of species-specific and pan-specific epitopes.
15. The method of claim 14 , wherein said RV strains are selected from the group consisting of RV species A, B, and C.
16. The method of claim 1 , wherein said RV peptide epitope is an RV-A16 peptide epitope.
17. The method of claim 16 , wherein said antigen-experienced RV-specific CD4 + T cells recognize conserved RV epitopes that respond to cross-reactive determinants of different RV strains.
18. The method of claim 17 , wherein said antigen-experienced RV-specific CD4 + T cells are epitope-specific T cells that are Th1-like and respond to RV infection.
19. The method of claim 17 , wherein said RV-A16-specific CD4 + T cells display a memory Th1 signature and respond rapidly to RV infection when contacted with an RV.
20. The method of 19 , wherein said RV is RV-A16 or RV-A39.
21. The method of claim 1 , wherein said method increases the number of CD4 + T cells that recognize conserved RV peptide epitopes.
22. The method of claim 21 , wherein said RV peptide epitope comprises a VP1 or VP2 peptide epitope.
23. The method of claim 1 , wherein said RV peptide epitopes are highly conserved across RV species A.
24. The method of claim 1 , wherein said method activates CD8 + T cells.
25. A method for increasing resistance to an RV infection in a subject in need thereof, said method comprising administering to said subject a composition consisting of a pharmaceutically-acceptable carrier, an adjuvant, and at least one RV peptide epitope selected from the group consisting of SEQ ID NOs:1-58, and biologically active fragments and homologs thereof, wherein at least one of said RV peptide epitopes is a conserved RV peptide epitope recognized by antigen-experienced RV-specific CD4 + T cells.
26. The method of claim 25 , wherein said composition comprises at least one RV peptide epitope selected from the group consisting of SEQ ID NOs:1-10.
27. The method of claim 26 , wherein said composition consists of SEQ ID NOs:1-10.
28. The method of claim 7 , wherein said at least one peptide consists of SEQ ID NO:3.
29. The method of claim 26 , wherein said at least one peptide consists of SEQ ID NO:3.