Multiple Infections with Seasonal Influenza A Virus Induce Cross-Protective Immunity against A(H1N1) Pandemic Influenza Virus in a Ferret Model

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.