| 摘要 |
Pandemic A(H1N1) continues its global spread, and vaccine production is a serious problem. Protection by current vaccines is limited by the mutational differences that rapidly accumulate in the circulating strains, especially in the virus surface proteins. New vaccine strategies are focusing at conserved regions of the viral internal proteins to produce T cell epitope-based vaccines. T cell responses have been shown to reduce morbidity and promote recovery in mouse models of influenza challenge. We previously reported 54 highly conserved sequences of NP, M1 and the polymerases of all human H1N1, H3N2, H1N2, and H5N1, and avian subtypes over the past 30 years. Sixty-three T cell epitopes elicited responses in HLA transgenic mice (A2, A24, B7, DR2, DR3 and DR4). These epitopes were compared to the 2007-2009 human H1N1 sequences to identify conserved and variant residues. Seventeen T cell epitopes of PB1, PB2, and M1 were selected as vaccine targets by analysis of sequence conservation and variability, functional avidity, non-identity to human peptides, clustered localization, and promiscuity to multiple HLA alleles. The vaccines composed of these epitopes, being highly conserved and temporally stable, would be useful for any avian or human influenza A virus.
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