Superior B. pertussis Specific CD4+ T-Cell Immunity Imprinted by Natural Infection

Pertussis remains endemic in vaccinated populations due to waning of vaccine-induced immunity and insufficient interruption of transmission. Correlates of long-term protection against whooping cough remain elusive but increasing evidence from experimental models indicates that the priming of particular lineages of B. pertussis (Bp) specific CD4+ T cells is essential to control bacterial load. Critical hallmarks of these protective CD4+ T cell lineages in animals are suggested to be their differentiation profile as Th1 and Th17 cells and their tissue residency. These features seem optimally primed by previous infection but insufficiently or only partially by current vaccines. In this review, evidence is sought indicating whether infection also drives such superior Bp specific CD4+ T cell lineages in humans. We highlight key features of effector immunity downstream of Th1 and Th17 cell cytokines that explain clearing of primary Bp infections in naïve hosts, and effective prevention of infection in convalescent hosts during secondary challenge. Outstanding questions are put forward that need answers before correlates of human Bp infection-primed CD4+ T cell immunity can be used as benchmark for the development of improved pertussis vaccines.