Identification of immunogenic consensus T-cell epitopes in globally distributed influenza-A H1N1 neuraminidase.
ABSTRACT Antigenic drift is the ability of the swine influenza virus to undergo continuous and progressive changes in response to the host immune system. These changes dictate influenza vaccine updates annually to ensure inclusion of antigens of the most current strains. The identification of those peptides that stimulate T-cell responses, termed T-cell epitopes, is essential for the development of successful vaccines. In this study, the highly conserved and specific epitopes from neuraminidase of globally distributed H1N1 strains were predicted so that these potential vaccine candidates may escape with antigenic drift. A total of nine novel CD8(+) T-cell epitopes for MHC class-I and eight novel CD4(+) T-cell epitopes for MHC class-II alleles were proposed as novel epitope based vaccine candidates. Additionally, the epitope FSYKYGNGV was identified as a highly conserved, immunogenic and potential vaccine candidate, capable for generating both CD8(+) and CD4(+) responses.
Article: Molecular docking analysis of 2009-H1N1 and 2004-H5N1 influenza virus HLA-B* 4405-restricted HA epitope candidates: implications for TCR cross-recognition and vaccine development[show abstract] [hide abstract]
ABSTRACT: Background The pandemic 2009-H1N1 influenza virus circulated in the human population and caused thousands deaths worldwide. Studies on pandemic influenza vaccines have shown that T cell recognition to conserved epitopes and cross-reactive T cell responses are important when new strains emerge, especially in the absence of antibody cross-reactivity. In this work, using HLA-B*4405 and DM1-TCR structure model, we systematically generated high confidence conserved 2009-H1N1 T cell epitope candidates and investigated their potential cross-reactivity against H5N1 avian flu virus. Results Molecular docking analysis of differential DM1-TCR recognition of the 2009-H1N1 epitope candidates yielded a mosaic epitope (KEKMNTEFW) and potential H5N1 HA cross-reactive epitopes that could be applied as multivalent peptide towards influenza A vaccine development. Structural models of TCR cross-recognition between 2009-H1N1 and 2004-H5N1 revealed steric and topological effects of TCR contact residue mutations on TCR binding affinity. Conclusions The results are novel with regard to HA epitopes and useful for developing possible vaccination strategies against the rapidly changing influenza viruses. Yet, the challenge of identifying epitope candidates that result in heterologous T cell immunity under natural influenza infection conditions can only be overcome if more structural data on the TCR repertoire become available.BMC Bioinformatics 01/2013; 14(Suppl 2):S21. · 2.75 Impact Factor