title: Cross-protective peptide vaccine against influenza A viruses developed in HLA-A*2402 human immunity model.
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.
  
  
  RESULTS
  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
  This CTL epitope peptide selection system can be used as an effective tool for the development of a cross-protective human influenza vaccine. Furthermore this vaccine strategy can be applicable to the development of all intracellular pathogens vaccines to induce epitope-specific CTL that effectively eliminate infected cells.
authors.affiliation: Department of Collaboration and Education, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ichihashi
authors.forename: Reiko
authors.initials: R
authors.lastname: Yoshida
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sugimoto
authors.forename: Ayato
authors.initials: A
authors.lastname: Takada
authors.forename: Kiichi
authors.initials: K
authors.lastname: Kajino
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D056738:Cross Protection / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D059871:HLA-A24 Antigen / Q000235:genetics / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology / Q000276:immunology / Q000472:pathogenicity; D053122:Influenza A Virus, H3N2 Subtype / Q000201:enzymology / Q000276:immunology / Q000472:pathogenicity; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology / Q000276:immunology / Q000472:pathogenicity; D009980:Influenza A virus / Q000201:enzymology / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009439:Neuraminidase / Q000276:immunology; D015203:Reproducibility of Results; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000939:Epitopes; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D022223:Vaccines, Subunit; C483468:hemagglutinin, human influenza A virus; D009439:Neuraminidase