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AssigneesUniversity of Virginia Patent Foundation, Benaroya Research Institute at Virginia Mason
InventorsJudith Ann Woodfolk, Lyndsey M. Muehling, William W. Kwok, Duy Tran Mai
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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.
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.
The method of 19, wherein said RV is RV-A16 or RV-A39.
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.
Dependencies are inferred from the claim text.