This is a prospective controlled human challenge study; Challenge group: The challenge volunteers will be healthy volunteers, aged 18-55 years, not having close contact with people having increased risk of severe pertussis complications or increased risk of transmitting to vulnerable individuals. Eligible volunteers must be willing to abide by infection control measures during social contact and to attend immediately if they become symptomatic. People who live in institutions in which multiple people share dormitory facilities, such as boarding schools or military barracks will be excluded.~The standard inoculum, a dose of 105 cfu, determined in Phase A of the Bp human challenge study, will be used. Participants will be followed up weekly and colonisation will be measured in nasal washes. If culture of the nasal wash taken at week 5 following nasal inoculation is positive for B. pertussis, then eradication therapy will be given at week 6. Early eradication therapy will be given if a participant presents with symptoms of early B. pertussis disease.~Recruitment will continue until 10 challenge volunteers have been colonised and then completed study participation to week 6 as per protocol. Volunteers who withdraw from the study early or have colonisation cleared with antibiotic treatment given for any reason will be replaced. Assuming a colonisation fraction of at least 30% and allowing for study withdrawal the investigator expect a maximum number of 36 volunteers to be inoculated.~Contact group: A group of contact volunteers, maximum 36 individuals, will be enrolled to assess transmission by monitoring for colonisation with the challenge strain of B. pertussis. These contact volunteers will be bedroom sharers of challenge volunteers and will give informed consent for their participation in the study, prior to inoculation of the corresponding challenge volunteer. Eradication therapy will be given at week 6 if the culture of nasal wash is positive for B. pertussis at week 5. Early eradication therapy will be given if a contact volunteer presents with symptoms of early B. pertussis disease.~Challenge and contact volunteers will be required to agree to infection control measures prior to enrolment in the study. Part of this agreement will be to refrain from bedroom sharing or intimate contact with any individual other than one declared and consented bedroom contact. They will avoid contact with children or people vulnerable to whooping cough such as unimmunised or partially immunised children and infants aged < 1 year, and pregnant women.
Primary objective- To assess the safety of nasal inoculation of healthy volunteers with B. pertussis with antibiotic therapy given to eradicate colonisation at 6 weeks after inoculation or at symptom onset, whichever occurs first~Secondary objectives - To measure the rate of natural clearance of carriage of B. pertussis following nasal inoculation~To assess the kinetics of B. pertussis colonisation density following nasal inoculation~To describe the microevolution of B. pertussis and adaptation of the resident microbiome during B. pertussis carriage~To measure B. pertussis-specific antibody and cellular immunological responses in healthy volunteers during colonisation with B. pertussis - To identify biomarkers that correlate with natural clearance of B. pertussis carriage after induced B. pertussis colonisation~To detect transmission of B. pertussis to bedroom contacts of inoculated volunteers during prolonged asymptomatic colonisation