Bordetella pertussis Infection: From Immune Pathogenesis to Next-Generation Vaccines

Pertussis is a highly contagious acute respiratory infection caused by Bordetella pertussis (B. pertussis), an exclusively human pathogen that remains a significant global public health concern despite widespread vaccination. Cyclical resurgences continue to occur, particularly in highly immunized populations, largely driven by waning immunity following acellular pertussis vaccination and persistent asymptomatic transmission among adolescents and adults. The pathogenesis of B. pertussis infection is mediated by a coordinated repertoire of adhesins and toxins that enable efficient colonization of the respiratory epithelium, disruption of mucociliary clearance, and profound modulation of host immune responses. Key virulence factors include pertussis toxin, adenylate cyclase toxin, and tracheal cytotoxin, which together impair innate immune defenses, alter leukocyte trafficking, suppress phagocytic function, and induce epithelial injury. While antibody-mediated immunity limits disease severity, it is insufficient to prevent colonization and onward transmission, underscoring the critical role of cell-mediated immunity. Protective clearance of infection is strongly associated with T helper 1 and T helper 17 immune responses, mucosal immunoglobulin A production, and the establishment of airway tissue-resident memory T cells—immune components that are suboptimally induced by current acellular vaccines. Advances in controlled human infection models have provided direct evidence that existing vaccines fail to prevent nasopharyngeal carriage, accelerating the development of next-generation vaccine strategies. These approaches aim to restore infection-like immune programming through mucosal delivery, enhanced innate immune activation, and broader antigenic presentation. Understanding the immune pathogenesis of B. pertussis infection provides a critical framework for redesigning vaccines capable of achieving durable, transmission-blocking immunity.