Vaccination with whole inactivated virus vaccine affects the induction of heterosubtypic immunity against influenza virus A/H5N1 and immunodominance of virus-specific CD8+ T-cell responses in mice

J Gen Virol. 2010 Jul;91(Pt 7):1743-53. doi: 10.1099/vir.0.020784-0. Epub 2010 Mar 24.


It was recently shown that the use of an experimental subunit vaccine protected mice against infection with a human A/H3N2 influenza virus, but consequently affected the induction of heterosubtypic immunity to a highly pathogenic A/H5N1 influenza virus, which was otherwise induced by the A/H3N2 infection. As whole inactivated virus (WIV) vaccines are widely used to protect against seasonal influenza and also contain inner viral proteins such as the nucleoprotein (NP), the potential of a WIV vaccine to induce protective immunity against infection was tested with a homologous A/H3N2 (A/Hong Kong/2/68) and a heterosubtypic A/H5N1 influenza virus (A/Indonesia/5/05). As expected, the vaccine afforded protection against infection with the A/H3N2 virus only. In addition, it was demonstrated that the use of WIV vaccine for protection against A/H3N2 infection affected the induction of heterosubtypic immunity that was otherwise afforded by A/H3N2 influenza virus infection. The reduction in protective immunity correlated with changes in the immunodominance patterns of the CD8(+) T-cell responses directed to the epitopes located in the acid polymerase subunit of the viral RNA polymerase (PA(224-233)) and the NP (NP(366-374)). In unvaccinated mice that experienced infection with the A/H3N2 influenza virus, the magnitude of the CD8(+) T-cell response to both peptides was similar on secondary infection with A/H5N1 influenza virus. In contrast, prior vaccination with WIV affected the immunodominance pattern and skewed the response after infection with influenza virus A/Indonesia/5/05 towards a dominant NP(366-374)-specific response. These findings may have implications for vaccination strategies aimed at the induction of protective immunity to seasonal and/or pandemic influenza.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antibody Specificity
  • CD8-Positive T-Lymphocytes / physiology*
  • Female
  • Immunodominant Epitopes
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Interferon-gamma
  • Lung / cytology
  • Lung / virology
  • Mice
  • Mice, Inbred C57BL
  • Specific Pathogen-Free Organisms
  • Spleen / cytology
  • Spleen / virology
  • Vaccination


  • Antibodies, Viral
  • Immunodominant Epitopes
  • Influenza Vaccines
  • Interferon-gamma