Vaccination against human influenza A/H3N2 virus prevents the induction of heterosubtypic immunity against lethal infection with avian influenza A/H5N1 virus

Rogier Bodewes, Joost H C M Kreijtz, Chantal Baas, Martina M Geelhoed-Mieras, Gerrie de Mutsert, Geert van Amerongen, Ron A M Fouchier, Albert D M E Osterhaus, Guus F Rimmelzwaan, JM van den Brand

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Annual vaccination against seasonal influenza viruses is recommended for certain individuals that have a high risk for complications resulting from infection with these viruses. Recently it was recommended in a number of countries including the USA to vaccinate all healthy children between 6 and 59 months of age as well. However, vaccination of immunologically naïve subjects against seasonal influenza may prevent the induction of heterosubtypic immunity against potentially pandemic strains of an alternative subtype, otherwise induced by infection with the seasonal strains. Here we show in a mouse model that the induction of protective heterosubtypic immunity by infection with a human A/H3N2 influenza virus is prevented by effective vaccination against the A/H3N2 strain. Consequently, vaccinated mice were no longer protected against a lethal infection with an avian A/H5N1 influenza virus. As a result H3N2-vaccinated mice continued to loose body weight after A/H5N1 infection, had 100-fold higher lung virus titers on day 7 post infection and more severe histopathological changes than mice that were not protected by vaccination against A/H3N2 influenza. The lack of protection correlated with reduced virus-specific CD8+ T cell responses after A/H5N1 virus challenge infection. These findings may have implications for the general recommendation to vaccinate all healthy children against seasonal influenza in the light of the current pandemic threat caused by highly pathogenic avian A/H5N1 influenza viruses.

Original languageEnglish
Pages (from-to)e5538
JournalPLoS One
Volume4
Issue number5
DOIs
Publication statusPublished - 2009

Keywords

  • Animals
  • CD8-Positive T-Lymphocytes
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Influenza A Virus, H3N2 Subtype
  • Influenza A Virus, H5N1 Subtype
  • Influenza Vaccines
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections
  • Vaccination

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