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

Many vaccines have heterogeneous 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 modelling framework to show that (i) the balance of how vaccines reduce transmission versus mortality and (ii) 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 in 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 the two classes of these vaccines may reduce disease symptoms without preventing infection and differ in their ability to reduce transmission. Furthermore, these findings point to the importance of generating precise predictions for virulence evolution in Bordetella pertussis (and other similar pathogens) by incorporating empirical characterizations of vaccine effects into models capturing the epidemiological details of this system.