Impact of vaccination on the speed of antigenic evolution

Abstract Rapidly evolving pathogens can escape antibody-mediated immunity, leading to recurrent epidemics. Vaccination is a key intervention to reduce infections and severe disease, yet concerns remain that it may accelerate antigenic evolution, potentially undermining long-term vaccine effectiveness. We developed a multi-strain mathematical model, parameterized for a rapidly evolving pathogen, to systematically explore how vaccination influences both the speed of antigenic evolution and the incidence of infection across a range of biological vaccine characteristics (efficacy, neutralization breadth, and vaccine strain) and implementation strategies (vaccination coverage and frequency). In the model, pathogen evolution is driven by cross-immunity and stochastic mutations in a one-dimensional antigenic space, and vaccination reduces an individual’s susceptibility to circulating strains according to the cross-immunity conferred by the vaccine strain. We find that vaccination generally reduces infection incidence, with higher coverage and efficacy leading to larger declines and, eventually, pathogen extinction. When transmission is substantially suppressed, antigenic evolution slows down. However, when vaccines match circulating strains but confer narrow cross-immunity, vaccination may accelerate antigenic evolution and potentially increase incidence. In a case study of seasonal influenza, vaccines with increased efficacy can speed up antigenic evolution but do not raise incidence. Overall, our results show that vaccination can effectively reduce both infection incidence and the speed of antigenic evolution in many scenarios. Nevertheless, the potential for vaccine-driven evolution warrants careful consideration, particularly when vaccine effectiveness in reducing incidence is limited.