Abstract
Vaccination is expected to reduce disease prevalence and to halt the spread of epidemics. Pathogen adaptation, however, may erode the efficacy of vaccination and limit our ability to control disease spread. Here, we examine the influence of the rate of vaccination of the host population on the overall risk of pathogen adaptation to vaccination. We extend the framework of evolutionary epidemiology theory to account for demographic stochasticity in the different steps leading to the adaptation to vaccination: (i) the introduction of a vaccine-escape variant by mutation from an endemic wild-type pathogen, (ii) the invasion of this vaccine-escape variant in spite of the risk of early extinction, (iii) the spread and fixation of the vaccine-escape variant in the pathogen population. We introduce a novel and versatile hybrid analytical-numerical method that allows fast computation of the probabilities associated with these steps. Using it, we show that increasing the rate of vaccination can reduce both the number of cases and the likelihood of pathogen adaptation. Our work clarifies the influence of vaccination policies-a major ecological perturbation of the environment of a pathogen-on different steps of pathogen adaptation. The model provides a useful theoretical framework to account for the interplay between epidemiology, selection and genetic drift and to anticipate the effects of public-health interventions on pathogen evolution.