Early Innate Immune Signatures Imprint Clinical Outcomes of Bordetella pertussis Challenge in a Controlled Human Infection Model

Background: Despite widespread vaccination, Bordetella pertussis (B. pertussis) continues to re-emerge globally, highlighting critical gaps in our understanding of vaccine-induced protective immunity. Controlled human infection models (CHIMs) offer a powerful platform to interrogate host-pathogen interactions in vivo, define correlates and mechanisms of protection, and inform next-generation pertussis vaccine design. Methods: This open label, phase 1, dose escalation CHIM trial (NCT05136599) was conducted at the Canadian Center for Vaccinology (Nova Scotia, Canada). Healthy adults aged 18-40 years with distinct infant vaccination histories (whole cell [wP] vs acellular [aP]) and low pre-exis