Seasonality as a driver of pH1N12009 influenza vaccination campaign impact

Although the most recent respiratory virus pandemic was triggered by a Coronavirus, sustained and elevated prevalence of highly pathogenic avian influenza viruses able to infect mammalian hosts highlight the continued threat of pandemics of influenza A virus (IAV) to global health. Retrospective analysis of pandemic outcomes, including comparative investigation of intervention efficacy in different regions, provide important contributions to the evidence base for future pandemic planning. The swine-origin IAV pandemic of 2009 exhibited regional variation in onset, infection dynamics and annual infection attack rates (IARs). For example, the UK experienced three severe peaks of infection over two influenza seasons, whilst Australia experienced a single severe wave. We adopt a seasonally forced 2-subtype model for the transmission of pH1N12009 and seasonal H3N2 to examine the role vaccination campaigns may play in explaining differences in pandemic trajectories in temperate regions. Our model differentiates between the nature of vaccine-and infection-acquired immunity. In particular, we assume that immunity triggered by infection elicits heterologous cross-protection against viral shedding in addition to long-lasting neutralising antibody, whereas vaccination induces imperfect reduction in susceptibility. We employ an Approximate Bayesian Computation (ABC) framework to calibrate the model using data for pH1N12009 seroprevalence, relative subtype dominance, and annual IARs for Australia and the UK. Heterologous cross-protection substantially suppressed the pandemic IAR over the posterior, with the strength of protection against onward transmission inversely correlated with the initial reproduction number. We show that IAV pandemic timing relative to the usual seasonal influenza cycle influenced the size of the initial waves of pH1N12009 in temperate regions and the impact of vaccination campaigns.