Natural immune boosting in pertussis dynamics and the potential for long-term vaccine failure

摘要

Incidence of whooping cough, unlike many other childhood diseases for which there is an efficacious vaccine, has been increasing over the past twenty years despite high levels of vaccine coverage. Its reemergence has been particularly noticeable among teenagers and adults. Many hypotheses have been put forward to explain these two patterns, but parsimonious reconciliation of clinical data on the limited duration of immunity with both pre- and postvac-cine era age-specific incidence remains a challenge. We consider the immunologically relevant, yet epidemiologically largely neglected, possibility that a primed immune system can respond to a lower dose of antigen than a naive one. We hypothesize that during the prevaccine era teenagers' and adults' primed immunity was frequently boosted by reexposure, so maintaining herd immunity in the face of potentially eroding individual immunity. In contrast, low pathogen circulation in the current era, except during epidemic outbreaks, allows immunity to be lost before reexposure occurs. We develop and analyze an age-structured model that encapsulates this hypothesis. We find that immune boosting must be more easily triggered than primary infection to account for age-incidence data. We make age-specific and dynamical predictions through bifurcation analysis and simulation. The boosting model proposed here parsimoniously captures four key features of pertussis data from highly vaccinated countries: (ⅰ) the shift in age-specific incidence, (ⅱ) reemergence with high vaccine coverage, (ⅲ) the possibility for cyclic dynamics in the pre- and postvac-cine eras, and (ⅳ) the apparent shift from susceptible-infectious-recovered (SIR)-like to susceptible-infectious-recovered-susceptible (SIRS)-like phenomenology of infection and immunity to Bordetella pertussis.