Repeated Bordetella pertussis Infections Are Required to Reprogram Acellular Pertussis Vaccine-Primed Host Responses in the Baboon Model

Background The United States has experienced a resurgence of pertussis following the 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 immune response to infection and test the ability of infection to reprogram aP-imprinted immune responses, we challenged unvaccinated and aP-vaccinated baboons with Bordetella pertussis multiple times and accessed the immune responses and outcomes of infections after each exposure.Results Multiple infections were required to elicit T-helper 17 responses and protection in aP-vaccinated animals comparable to responses seen in unvaccinated animals after a single challenge. Even after 3 challenges, T-helper 1 responses were not observed in aP-vaccinated animals. Immunoglobulin G responses to vaccine and nonvaccine antigens were not negatively affected in aP-vaccinated animals.Conclusions 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 that 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. We evaluated the impact of acellular vaccination on the response to Bordetella pertussis infection. T-cell responses associated with clearance were reduced in aP-vaccinated baboons. Multiple infections were required to reprogram the aP-vaccine response to a response capable of preventing infection.

Automated summary

The resurgence of pertussis in the United States is likely due to the failure of acellular pertussis (aP) vaccines to provide long-lasting immunity and prevent infection, carriage, and transmission. By studying baboons, it was found that multiple infections were necessary to induce immune responses and protection in aP-vaccinated animals comparable to those seen in unvaccinated animals after a single challenge. Immunoglobulin G responses to vaccine and nonvaccine antigens were not negatively affected in aP-vaccinated animals. The results suggest the possibility of reprogramming aP-primed immune responses through optimal boosters and multiple doses.