Controlled human infection with Bordetella pertussis induces asymptomatic, immunising colonisation

RATIONALE: Bordetella pertussis is one of the leading causes of vaccine preventable death and morbidity globally. Human asymptomatic carriage as a reservoir for community transmission of infection might be a target of future vaccine strategies but has not been demonstrated to occur. OBJECTIVE: To demonstrate that asymptomatic nasopharyngeal carriage of Bordetella pertussis is inducible in humans and to define microbiological and immunological features of pre-symptomatic infection. METHODS: Healthy subjects aged 18-45 years with an anti-pertussis toxin IgG concentration of <20 IU/ml were inoculated intranasally with non-attenuated, wild type Bordetella pertussis strain B1917. Safety, colonisation and shedding were monitored over 17 days in an in-patient facility. Colonisation was assessed by culture and qPCR. Azithromycin was administered from day 14. The inoculum dose was escalated aiming to colonise at least 70% of participants. Immunological responses were measured. RESULTS: 34 participants were challenged in groups of four or five. The dose was gradually escalated from 103 colony forming units (0% colonised) to 105 colony forming units (80% colonised). Minor symptoms were reported in a minority of participants. Azithromycin eradicated colonisation in 48 hours in 88% of colonised individuals. Anti-pertussis toxin IgG seroconversion occurred in nine out of 19 colonised participants and in none of the participants who were not colonised. Nasal wash was a more sensitive method to detect colonisation than pernasal swabs. No shedding of Bordetella pertussis was detected in systematically collected environmental samples. INTERPRETATION: Bordetella pertussis colonisation can be deliberately induced and leads to a systemic immune response without causing pertussis symptoms.ClinicalTrials.gov:NCT03751514.