Why is the incidence of infection with 2009 H1N1 influenza highest among 5-24 year olds, and lowest in those over 65 years of age? Were the oldsters previously infected with a related influenza virus, or is there another explanation?
The sera of individuals born in the early part of the 20th century have antibodies that block infection with the 2009 H1N1 virus. We also know that antibodies that prevent infection with recently circulating seasonal H1N1 viruses do not react with pandemic H1N1 strains. These findings may partly explain the lower incidence of influenza this year in individuals greater than 65 years of age (illustrated).
But other factors might also be responsible for safeguarding the older population. Infection of guinea pigs with a 2007 seasonal H1N1 virus confers some protection against infection 3 weeks later with a 2009 H1N1 strain. The animals produced significantly less virus in their respiratory tracts, and transmission of infection to naive animals was impaired. The pre-inoculated animals were also less susceptible to acquiring the 2009 H1N1 virus from another infected guinea pig. Similar results were observed when guinea pigs were first inoculated with a seasonal H3N2 strain and challenged with the pandemic virus. The conclusion is that infection with seasonal H1N1 or H3N2 viruses provides protection against infection with the 2009 H1N1 strain.
The protective effect of the seasonal strains does not appear to involve neutralizing antibodies. Sera from the guinea pigs inoculated with the seasonal H1N1 or H3N2 strains did not contain antibodies with hemagglutination-inhibition (HI) activity against 2009 H1N1 virus. One explanation for the protective response is that the initial infection leads to T cells or antibodies that recognize protein sequences that are shared among different influenza virus strains or even subtypes. This so-called ‘heterosubtypic’ or ‘cross-protective’ immunity is often observed in animal models of influenza.
Can these results extrapolated to humans – in other words, might transmission of the 2009 H1N1 influenza virus in the human population be slowed by previous exposure to seasonal strains? One good example of heterosubtypic immunity after influenza virus infection in humans was provided by analysis of archival records from the 1957 pandemic in Cleveland, Ohio. That outbreak was triggered when the seasonal H1N1 strains were replaced by a novel H2N2 strain. Only 5.6% of the adults who had had influenza before 1957 developed influenza during the pandemic. In contrast, 55.2% of the children who had influenza before 1957 contracted it afterwards. These findings suggest that accumulated heterosubtypic immunity might have an impact on influenza during a pandemic.
The emergence of 2009 H1N1 influenza is a good opportunity to study the effect of heterosubtypic immunity because the strain is antigenically very different from previously circulating seasonal H1N1 and H3N2 strains.
Steel J, Staeheli P, Mubareka S, García-Sastre A, Palese P, & Lowen AC (2009). Transmission of pandemic H1N1 influenza virus and impact of prior exposure to seasonal strains or interferon treatment. Journal of Virology PMID: 19828604.
Epstein, S. (2006). Prior H1N1 Influenza Infection and Susceptibility of Cleveland Family Study Participants during the H2N2 Pandemic of 1957: An Experiment of Nature The Journal of Infectious Diseases, 193 (1), 49-53 DOI: 10.1086/498980.