Immunoinformatics analysis of H5N1 proteome for designing an epitope-derived vaccine and predicting the prevalence of pre-existing cellular-mediated immunity toward bird flu virus in Indonesian population
Background The persistence of influenza A virus H5N1 among poultry in Indonesia, along with increasing numbers of human infections by this virus, point to risk of a reassortment event with other prevalent influenza A sub-types in Indonesia. In the absence of cross-protective antibody to the emerging strain, the presence of cel-lular immunity might reduce the influenza illness to subclinical level and could dampen the pandemic. This study evaluated the degree of likely cross-protective T-cell mediated immunity against such hypothetical emerging influenza A strains. All 11 protein sequences from Indonesian H5N1 isolates were evaluated for the presence of T-cell epitopes restricted by Indonesian HLA types.
Results Among 4433 possible nonamer peptides, 225 were predicted as good CTL epitopes (score < 1%) by NetCTLpan and had strong binding affinity (IC50 < 50 nM) toward HLA molecules by IEDBann and netMHCann. Epitope conservation analysis revealed that at least 60% of the H5N1 Indonesian isolates contained the identical sequences of this 225 peptide set. Sixty-nine peptides were specific for H5N1 and 156 were cross-reactive with other subtypes. Significant numbers (184) of peptides bound to more than one HLA allele (promiscuous). Blast analysis showed that the majority (213) of peptides did not have similarity with the human self peptides likely to induce autoimmunity if used for vaccination. Certain peptides can act as a core for HLA Class II molecules, and some superimposed with the putative linear B-cell epitopes. Eighteen peptides emerged as likely vaccine components optimized to an Indonesian population but likely also to be effective among most other ethnic groups.
Conclusions Routine exposure to seasonal influenza A likely ensures some level of cross-protective immunity to H5N1 and most reassortment mutants. Identifying of such likely cross-reactive T-cell epitopes may aid in gauging the threat of potential outbreaks and composing the vaccines that could contain them.