Estimation of age-specific susceptibility to influenza in the Netherlands and its relation to loss of CD8+ T-cell memory

Abstract

The magnitude of influenza epidemics is largely determined by the number of susceptible individuals at the start of the influenza season. Susceptibility, in turn, is influenced by antigenic drift. The evolution of influenzas B-cell epitopes has been charted thoroughly, and only recently evidence for T-cell driven evolution is accumulating. We investigate the relation between susceptibility to influenza, and antigenic drift at CD8+ T-cell epitopes over a 45-year timespan. We estimate age-specific susceptibility with data reported by general practitioners, using a disease-transmission model in a Bayesian framework. We find large variation in susceptibility, both between seasons and age classes. Although it is often assumed that antigenic drift drives the variation in susceptibility, we do not find evidence for a relation between drift and susceptibility in our data. This suggests that other factors determining the variation in susceptibility play a dominating role, or that complex influenza-infection histories obscure any direct effects.\n\nPreface to this bioR{chi}iv pre-printWe are currently in the process of making this manuscript ready for re-submission, and are resolving some issues brought forward by our referees. Most importantly, we aim to better incorporate the co-circulation of the various influenza A and B subtypes during the different seasons, both in the estimation of susceptibility and antigenic drift.