Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
J Infect Dis. 2024 Feb 14;229(2):376-383. doi: 10.1093/infdis/jiad332.
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.
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.
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.
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.
在美国，在引入无细胞百日咳（aP）疫苗后，百日咳再次爆发。这可能是由于 aP 疫苗未能诱导持久免疫，无法预防感染、携带和传播。
为了评估 aP 疫苗接种对感染免疫反应的影响，并测试感染重新编程 aP 印迹免疫反应的能力，我们多次用百日咳博德特氏菌挑战未接种疫苗和 aP 疫苗接种的狒狒，并在每次暴露后评估免疫反应和感染结果。
多次感染才能在 aP 疫苗接种动物中引起与单次挑战后未接种疫苗动物相当的 T 辅助 17 反应和保护。即使在 3 次挑战后，aP 疫苗接种动物中也未观察到 T 辅助 1 反应。aP 疫苗接种动物的疫苗和非疫苗抗原的免疫球蛋白 G 反应不受影响。
我们的结果表明，可以重新训练 aP 免疫反应，但可能需要最佳的加强针和多次剂量。我们在狒狒模型中的结果表明，aP 疫苗接种人群中百日咳博德特氏菌的循环集中在人群的年轻年龄段，为改进 aP 疫苗接种人群中百日咳博德特氏菌流行病学的建模提供了信息。
