Immunological insights into why pertussis continues to be endemic.

Pertussis (whooping cough) is a vaccine-preventable bacterial disease caused by Bordetella pertussis. Despite widespread vaccination, cases have increased globally since the 1990s, with notable outbreaks in 2012, 2016, and following the COVID-19 pandemic. Persistent endemicity and periodic epidemics are driven by limited prevention of nasal colonization, waning immunity after vaccination or natural infection, and pathogen adaptation. Differences between acellular (aP) and whole-cell (wP) vaccines reflect distinct immune profiles, with aP vaccines favoring Th2 responses and wP vaccines inducing Th1/Th17 responses and tissue-resident memory T cells. Circulating strains have evolved under vaccine pressure, including shifts in ptxP, ptxA and prn alleles, increasing pertussis toxin production, emergence of pertactin-deficient variants, and rising macrolide resistance linked to 23S rRNA mutations. Optimizing current vaccine strategies and developing next-generation vaccines that improve durable, Th1/Th17-polarized immunity and reduce transmission are essential for enhanced pertussis control.