Abstract
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.
Original language | English |
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Pages (from-to) | 1743-53 |
Number of pages | 11 |
Journal | Journal of General Virology |
Volume | 91 |
Issue number | Pt 7 |
DOIs | |
Publication status | Published - Jul 2010 |
Keywords
- Animals
- Antibodies, Viral
- Antibody Specificity
- CD8-Positive T-Lymphocytes
- Female
- Immunodominant Epitopes
- Influenza A Virus, H3N2 Subtype
- Influenza A Virus, H5N1 Subtype
- Influenza Vaccines
- Interferon-gamma
- Lung
- Mice
- Mice, Inbred C57BL
- Specific Pathogen-Free Organisms
- Spleen
- Vaccination