Seasonal Influenza Vaccination and the 2009 Pandemic

TO THE EDITOR—We were pleased to see the editorial by Glezen [1], which outlined a hypothesis to explain the observation made by Cowling and colleagues [2] in the same issue of the Journal that receipt of the seasonal trivalent influenza vaccine (TIV) appeared to increase the risk of infection with pandemic influenza 2009 (pH1N1). This observation has been made previously, but the effect size has varied. Four studies from Canada reported odds ratios (OR) for pH1N1 infection following receipt of seasonal TIV in the range 1.4–2.5 (confidence interval [CI] = 1.03–2.74) [3], whereas the Hong Kong investigators reported a nonsignificant increased risk, with an OR = 1.11 (.54–2.26) [2]. Investigators in Australia reported an OR = .97 (.60–1.56) [4]. The timing of the pandemic compared to the previous influenza season provides a possible explanation of these apparently discrepant findings. Although not yet a fully accepted phenomenon, there is a growing body of evidence that infection with one strain of influenza gives a “short-lived strain transcending immunity” [5]. This concept of heterosubtypic temporary immunity is a necessary inclusion for models to reproduce the observed influenza phylogenetic structures [5, 6] and has recently been used by us to model and explain the apparent increased risk of infection with pH1N1 following receipt of seasonal TIV [7, 8]. There is evidence for temporary immunity from human studies during the 1957 H2N2 pandemic [9] and the reemergence of H1N1 in 1977–1978 [10]. Temporary heterosubtypic immunity is thought to last 3–6 months, but the evidence for its duration is derived from the modeling literature [5] and needs additional investigation.