Multiple infections with seasonal influenza A virus induce cross-protective immunity against A(H1N1) pandemic influenza virus in a ferret model

J Infect Dis. 2010 Oct 1;202(7):1011-20. doi: 10.1086/656188.


Background: An age bias toward children and young adults has been reported for infection and hospitalizations with pandemic H1N1 influenza (A[H1N1]pdm) in the 2009 and 2010 influenza seasons in the Southern and Northern Hemispheres. Serological analysis of prepandemic samples has shown a higher incidence of cross-reactive antibodies to A(H1N1)pdm virus in older populations; conserved T cell epitopes between viruses have been identified. The contribution of preexisting immunity to seasonal influenza to protection against A(H1N1)pdm infection was analyzed in a ferret model.

Methods: Ferrets were pre-infected with influenza A viruses and/or vaccinated with inactivated influenza viruses with adjuvant. Infection after challenge was assessed by measuring shedding virus, transmission to naive animals, and seroconversion.

Results: Homologous vaccination reduced the incidence of infection and delayed transmission. Pre-infection with virus induced sterilizing immunity to homologous challenge. One prior infection with seasonal influenza A virus improved clearance of A(H1N1)pdm virus. Prior infection with A(H1N1)pdm virus reduced shedding after seasonal influenza A challenge. Two infections with seasonal influenza A viruses reduced the incidence of infection, the amount and duration of virus shedding, and the frequency of transmission following A(H1N1)pdm challenge.

Conclusion: These data suggest the reduced incidence and severity of infection with A(H1N1)pdm virus in the adult population during the 2009-2010 influenza season may be a result of previous exposure to seasonal influenza A viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood*
  • Antibodies, Viral / immunology*
  • Cross Protection*
  • Ferrets
  • Immunization, Secondary / methods
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / virology
  • Vaccination / methods


  • Antibodies, Viral
  • Influenza Vaccines