CD4+ T-cell immunity to Bordetella pertussis

Despite widespread immunization, Bordetella pertussis (B. pertussis) cases are resurging worldwide, prompting renewed interest in understanding the key mechanisms that underlie protective immunity. Similar to natural infection, immunization with whole-cell pertussis vaccines (wPV) generates long-lasting T_H1/T_H17 CD4 + T-cell responses that protect against B. pertussis infection. Additionally, wPV immunization generates robust tissue-resident memory T-cell responses (T_RM) that limit both pertussis disease and transmission. In contrast, acellular pertussis vaccines (aPV) generate short-lived T_H2-polarized immune responses that confer protection against severe disease but do not prevent B. pertussis colonization or transmission. Furthermore, the circulation of clinical strains with varied expression of aPV antigens also highlights the need for next-generation pertussis vaccines. Thus, coordinated innate and adaptive immune responses at the site of infection are required to effectively protect against B. pertussis colonization and persistence. This review integrates our current knowledge of natural and vaccine mediated T-cell immunity from both animal models and human studies to guide the development of improved pertussis vaccines capable of combating the resurgence of pertussis.