cross-protective peptide vaccine against influenza a viruses developed in hla-a2402 human immunity modelcross-protective肽疫苗开发的a型流感病毒hla-a2402人工免疫模型.pdfVIP

Cross-Protective Peptide Vaccine against Influenza A Viruses Developed in HLA-A*2402 Human Immunity Model 1 2 1 2 1 Toru Ichihashi , Reiko Yoshida , Chihiro Sugimoto , Ayato Takada , Kiichi Kajino * 1 Department of Collaboration and Education, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan, 2 Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan Abstract Background: The virus-specific cytotoxic T lymphocyte (CTL) induction is an important target for the development of a broadly protective human influenza vaccine, since most CTL epitopes are found on internal viral proteins and relatively conserved. In this study, the possibility of developing a strain/subtype-independent human influenza vaccine was explored by taking a bioinformatics approach to establish an immunogenic HLA-A24 restricted CTL epitope screening system in HLA- transgenic mice. Methodology/Principal Findings: HLA-A24 restricted CTL epitope peptides derived from internal proteins of the H5N1 highly pathogenic avian influenza A virus were predicted by CTL epitope peptide prediction programs. Of 35 predicted peptides, six peptides exhibited remarkable cytotoxic activity in vivo. More than half of the mice which were subcutaneously vaccinated with the three most immunogenic and highly conserved epitopes among three different influenza A virus subtypes (H1N1, H3N2 and H5N1) survived lethal influenza virus challenge during both effector and memory CTL phases. Furthermore, mice that were intranasally vaccinated with these peptides remained free of clinical signs after lethal virus challenge during the effector phase. Conclusions/