Methods: In this first-in-human controlled infection model healthy volunteers aged 18-45 years with an anti-pertussis toxin (PT) IgG level of <20 IU/mL were inoculated intranasally with Bp strain B1917. Safety, colonization and shedding were monitored over a 17 day inpatient period. Colonization was assessed by culture and qPCR of nasal washes and nasopharyngeal swabs. Azithromycin eradication therapy was commenced on day 14. The dose of inoculum was escalated to optimize colonization rate, expressed as the percentage of volunteers colonized at any sampling point between day 3 and 14. The immunological response is being assessed at various time-points over one year.
Results: 24 volunteers were challenged in groups of 4-5. The dose was gradually escalated from 103 colony forming units (cfu) to 105 cfu. Colonization rate ranged from 0% (dose 103 cfu) to 80% (105 cfu). Amongst this initial cohort, no significant safety concerns or symptoms attributed to Bp disease were reported. Eradication was achieved by 48 hours in 100% of colonized volunteers. At least four fold rise in anti-PT IgG by day 28 in comparison to baseline was observed in five out of eight volunteers who had >1000 cfu/mL viable Bp in the nasal wash and in one volunteer without detectable colonization. Nasal wash cultures were more sensitive in detecting colonization than nasopharyngeal swab cultures. No shedding of Bp was detected in systematically collected environmental samples.
Conclusion: This is the first study to demonstrate safe deliberate induction of Bp colonization. It shows that asymptomatic Bp colonization occurs, and causes a systemic immune response. The model that we have developed will be a valuable tool to further investigate Bp colonization and vaccine development.
H. De Graaf,
A. Hill, None
D. Gbesemete, None
A. Gorringe, None
D. Diavatopoulos, None
K. Kester, Sanofi: Employee , Salary .
G. Berbers, None
S. Faust, Pfizer, Merck, Sanofi, AstraZeneca/Medimmune: Scientific Advisor , all honoraria paid to institution with no personal payments of any kind .
R. Read, None