Abstract
Protective immunity wanes rapidly after immunization of children with acellular pertussis (aP) vaccines and these vaccines do not prevent nasal colonization or transmission of Bordetella pertussis in baboons. In this study, we examined the role of tissue-resident memory T (TRM) cells in persistent protective immunity induced by infection or immunization with aP and whole-cell pertussis (wP) vaccines in mice. Immunization of mice with a wP vaccine protected against lung and nasal colonization, whereas an aP vaccine failed to protect in the nose. IL-17 and IFN-γ-secreting CD69+CD4+ TRM cells were expanded in the lung and nasal tissue after B. pertussis challenge of mice immunized with wP, but not aP vaccines. However, previous infection induced the most persistent protection against nasal colonization and this correlated with potent induction of nasal tissue TRM cells, especially IL-17-secreting TRM cells. Blocking T cell migration to respiratory tissue during immunization with a wP vaccine impaired bacterial clearance, whereas transfer of TRM cells from convalescent or wP-immunized mice conferred protection to naïve mice. Our findings reveal that previous infection or wP vaccination are significantly more effective than aP vaccination in conferring persistent protective immunity against B. pertussis and that this is mediated by respiratory TRM cells.