Speaker
Description
Vaccine-induced immunity is rarely static; rather, an individual's immune state is fundamentally shaped by their unique history of pathogen exposures. Silent exposures to the pathogen may lead to "immune boosting," reinforcing immunity without causing symptomatic infection. Moreover, because a primed immune system can respond to a lower dose of antigen than a naive one, immune boosting can be triggered by exposures that are too weak to lead to productive infection. Recent analyses of pertussis dynamics suggest that such extensive immune priming has significant implications for population-level vaccine effectiveness. Nevertheless, the population-level implications of immune boosting and immunological priming are not well understood and remain largely unexplored.
In this work, we incorporate a `strong' form of immune boosting and the mechanism of immunological priming into a leaky-vaccine SIR model. Our analysis reveals a fundamental relationship between the individual probability of boosting and the population-level impact of vaccination. As expected, we show that immune boosting enhances vaccine effectiveness in a wide range of scenarios. Surprisingly, we demonstrate that when immune priming is extensive, vaccine effectiveness can paradoxically decrease with increasing vaccine coverage. Furthermore, we show that in high-transmission settings, VE becomes independent of vaccine coverage. We elucidate these counterintuitive behaviors using a complementary analysis of repeated pathogen exposures and an analysis of direct and indirect effects. Our work sheds light on the complex interplay between individual immune history and herd immunity, emphasizing the importance of accounting for immunological priming when evaluating vaccine impact.
