%0 Journal Article %A Bodewes, Rogier %A Kreijtz, Joost H. C. M. %A Hillaire, Marine. L. B. %A Geelhoed-Mieras, Martina M. %A Fouchier, Ron A. M. %A Osterhaus, Albert D. M. E. %A Rimmelzwaan, Guus F. %T 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 %D 2010 %J Journal of General Virology, %V 91 %N 7 %P 1743-1753 %@ 1465-2099 %R https://doi.org/10.1099/vir.0.020784-0 %I Microbiology Society, %X 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 (PA224–233) and the NP (NP366–374). 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 NP366–374-specific response. These findings may have implications for vaccination strategies aimed at the induction of protective immunity to seasonal and/or pandemic influenza. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.020784-0