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
Healthy adults aged 18 to 55 years inclusive on the day of screening
Fully conversant in the English language
Able to communicate easily by both mobile telephone, email and text messaging
Able and willing (in the investigator's opinion) to comply with all study requirements
unimmunised or partially immunised children and infants aged < 1 year
pregnant women >32 weeks who have not received pertussis vaccination at least a week prior to contact
immunosuppressed individuals
frail individuals
Parallel
Bordetella pertussis B1917
Biological/VaccineThe B. pertussis isolate to be used in this human colonisation model is strain B1917, which is representative of current isolates in Europe. The strain, isolated in 2000 from a Dutch patient with B. pertussis disease, expresses Pertactin (PRN), Pertussis Toxin (PT) and Filamentous Haemagglutinin (FHA). This strain has been extensively characterised in the mouse model as well as by proteomics and transcriptomics and has a closed genome available. It is fully sensitive to azithromycin in vitro.
Azithromycin Pill
DrugA 3 day course of azithromycin will be administered to all colonised volunteers at week 6, or sooner if early pertussis disease is suspected
To assess the incidence of solicited adverse events during prolonged colonisation with Bordetella pertussis following nasal inoculation of healthy adult volunteers
• Participants will be asked about the occurrence of solicited adverse events at standardised visits. Any symptoms will be recorded and assessed by a study doctor. If deemed necessary by the study doctor further tests will be requested
To assess the incidence of unsolicited adverse events during prolonged colonisation with Bordetella pertussis following nasal inoculation of healthy adult volunteers
Participants will be asked about the occurrence of unsolicited adverse events at standardised visits. Any symptoms will be recorded and assessed by a study doctor. If deemed necessary by the study doctor further tests will be requested
To establish the rate of natural clearance of Bordetella pertussis colonisation as detected by nasal wash.
Bordetella pertussis colonisation will be measured weekly by culture of nasal washes. Putative positive cultures will be confirmed by polymerase chain reaction (PCR).
To establish the rate of natural clearance of Bordetella pertussis colonisation as detected by nasopharyngeal swab
Bordetella pertussis colonisation will be measured weekly by culture of nasopharyngeal swabs. Putative positive cultures will be confirmed by polymerase chain reaction (PCR).
To establish the change in colonisation density of Bordetella pertussis during prolonged colonisation as measured from nasal wash samples
Bordetella pertussis colonisation density will be measured weekly by culture of nasal washes. Putative positive cultures will be confirmed by polymerase chain reaction (PCR).
To establish the change in colonisation density of Bordetella pertussis during prolonged colonisation as measured by nasopharyngeal swab samples
Bordetella pertussis colonisation density will be measured weekly by culture of nasopharyngeal swabs. Putative positive cultures will be confirmed by polymerase chain reaction (PCR).
To establish the occurrence of transmission to close contacts during prolonged Bordetella pertussis colonisation
Bordetella pertussis colonisation density will be measured weekly by culture of nasal washes. Putative positive cultures will be confirmed by polymerase chain reaction (PCR).
To establish any association between baseline anti-PT IgG level and protection from colonisation with Bordetella pertussis
Anti-PT IgG will be measured in blood at baseline (Day 0)
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