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.
