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

• Published in: Journal of general virology Vol. 91; no. Pt 7; pp. 1743 - 1753
• Main Authors: Bodewes, Rogier, Kreijtz, Joost H C M, Hillaire, Marine L B, Geelhoed-Mieras, Martina M, Fouchier, Ron A M, Osterhaus, Albert D M E, Rimmelzwaan, Guus F
• Format: Journal Article
• Language: English
• Published: England 01.07.2010
• Subjects: Animals; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antibody Specificity; CD8-Positive T-Lymphocytes - physiology; Female; Immunodominant Epitopes; Influenza A virus; Influenza A Virus, H3N2 Subtype - immunology; Influenza A Virus, H5N1 Subtype - immunology; Influenza Vaccines - immunology; Influenza virus; Interferon-gamma; Lung - cytology; Lung - virology; Mice; Mice, Inbred C57BL; Specific Pathogen-Free Organisms; Spleen - cytology; Spleen - virology; Vaccination
• ISSN: 0022-1317; 1465-2099; 1465-2099
• DOI: 10.1099/vir.0.020784-0

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.