Vaccine driven virulence evolution: Consequences of unbalanced reductions in mortality and transmission and implications for pertussis vaccines

Many vaccines have heterogenous effects across individuals. Additionally, some vaccines do not prevent infection, but reduce disease-associated mortality and transmission. Both of these factors will alter selection pressures on pathogens, and thus shape the evolution of pathogen virulence. We use a mathematical modeling framework to show that 1. the balance of how vaccines reduce transmission vs. mortality, and 2. individual variability in protection conferred, both shape the evolution of pathogen virulence. Epidemiological (burden of disease) and evolutionary (pathogen virulence) outcomes are both worse when vaccines confer smaller reductions in transmission than mortality. Furthermore, outcomes are modulated by variability in vaccine effects, with increased variability limiting the extent of virulence evolution but in some cases preventing eradication. These findings are pertinent to current concerns about the global resurgence of pertussis and the efficacy of pertussis vaccines, as t...