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BACKGROUND: The US has experienced a resurgence of pertussis following introduction of acellular pertussis (aP) vaccines. This is likely due to the failure of aP vaccines to induce durable immunity and prevent infection, carriage, and transmission.

METHODS: To evaluate the impact of aP-vaccination on the host immune response to infection and test the ability of infection to reprogram aP-imprinted immune responses, we challenged unvaccinated and aP-vaccinated baboons with B. pertussis multiple times and accessed the immune responses, and outcomes of infections, in both groups following each exposure.

RESULTS: Multiple infections were required to elicit Th17 responses and protection in aP-vaccinated animals comparable to responses seen in unvaccinated animals following a single challenge. Even following three challenges, Th1 responses were not observed in aP-vaccinated animals. IgG responses to vaccine and non-vaccine antigens were not negatively impacted in aP-vaccinated animals.

CONCLUSION: Our results indicate that it is possible to retrain aP-primed immune responses but it will likely require an optimal booster and multiple doses. Our results in the baboon model suggest circulation of B. pertussis in aP-vaccinated populations is concentrated in the younger age-bands of the population providing information that can guide improved modeling of B. pertussis epidemiology in aP-vaccinated populations.