Does homologous reinfection drive multiple-wave influenza outbreaks? Accounting for immunodynamics in epidemiological models()

Epidemiological models of influenza transmission usually assume that recovered individuals instantly develop a fully protective immunity against the infecting strain. However, recent studies have highlighted host heterogeneity in the development of this immune response, characterized by delay and even absence of protection, that could lead to homologous reinfection (HR). Here, we investigate how these immunological mechanisms at the individual level shape the epidemiological dynamics at the population level. In particular, because HR was observed during the successive waves of past pandemics, we assess its role in driving multiple-wave influenza outbreaks. We develop a novel mechanistic model accounting for host heterogeneity in the immune response. Immunological parameters are inferred by fitting our dynamical model to a two-wave influenza epidemic that occurred on the remote island of Tristan da Cunha (TdC) in 1971, and during which HR occurred in 92 of 284 islanders. We then explore the dynamics predicted by our model for various population settings. We find that our model can explain HR over both short (e.g. week) and long (e.g. month) time-scales, as reported during past pandemics. In particular, our results reveal that the HR wave on TdC was a natural consequence of the exceptional contact configuration and high susceptibility of this small and isolated community. By contrast, in larger, less mixed and partially protected populations, HR alone cannot generate multiple-wave outbreaks. However, in the latter case, we find that a significant proportion of infected hosts would remain unprotected at the end of the pandemic season and should therefore benefit from vaccination. Crucially, we show that failing to account for these unprotected individuals can lead to large underestimation of the magnitude of the first post-pandemic season. These results are relevant in the context of the 2009 A/H1N1 influenza post-pandemic era.