Human pertussis challenge study identifies plausible correlates of protection—but only in a whole-cell-primed generation

Summary Two Lancet Microbe papers together present and contextualize a controlled human infection model for Bordetella pertussis in healthy adults. The primary study showed that outpatient intranasal challenge with CFU was feasible and safe in 50 evaluable adults aged 18–55 years, with 20 participants (40%) becoming asymptomatically colonized, no serious adverse events, and no detected transmission to 14 monitored close contacts. Participants who resisted colonization had higher pre-inoculation serum IgG against pertussis toxin, pertactin, and filamentous haemagglutinin, stronger serum and mucosal IgA binding to whole B pertussis, and higher Th22-associated IL-22 responses, while previously colonized participants were less likely to be recolonized after rechallenging about 90 days later. The accompanying correspondence argues that these candidate correlates of protection should be interpreted cautiously because all participants in the human challenge study had been primed in childhood with whole-cell pertussis vaccines. Since whole-cell and acellular priming may shape durable, yet distinct immune responses into...