Investigating Bordetella pertussis colonisation and immunity: protocol for an inpatient controlled human infection model

• Published in: BMJ open Vol. 7; no. 10; p. e018594
• Main Authors: de Graaf, Hans, Gbesemete, Diane, Gorringe, Andrew R., Diavatopoulos, Dimitri A., Kester, Kent E., Faust, Saul N., Read, Robert C.
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.10.2017; BMJ Publishing Group
• Subjects: Adults; Antibiotics; Bacterial infections; Bordetella pertussis - isolation & purification; Bordetella pertussis - physiology; Clinical Protocols; Disease; Dose-Response Relationship, Immunologic; Health care; Humans; Immunity (Disease); Infections; Infectious Diseases; Pathogenesis; Pertussis Vaccine - administration & dosage; Pertussis Vaccine - immunology; Public health; Research Design; Tropical diseases; Vaccination; Vaccines; Vaccines, Acellular - administration & dosage; Vaccines, Acellular - immunology; Volunteers; Whooping cough; Whooping Cough - immunology; Whooping Cough - prevention & control; United Kingdom > UK; England; China; whooping cough; colonisation; human challenge study; vaccine development; bordetella pertussis
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2017-018594

IntroductionWe summarise an ethically approved protocol for the development of an experimental human challenge colonisation model. Globally Bordetella pertussis is one of the leading causes of vaccine-preventable death. Many countries have replaced whole cell vaccines with acellular vaccines over the last 20 years during which pertussis appears to be resurgent in a number of countries in the developed world that boast high immunisation coverage. The acellular vaccine provides relatively short-lived immunity and, in contrast to whole cell vaccines, may be less effective against colonisation and subsequent transmission. To improve vaccine strategies, a greater understanding of human B. pertussis colonisation is required. This article summarises a protocol and does not contain any results.Methods and analysisA controlled human colonisation model will be developed over two phases. In phase A, a low dose of the inoculum will be given intranasally to healthy participants. This dose will be escalated or de-escalated until colonisation is achieved in approximately 70% (95% CI 47% to 93%) of the exposed volunteers without causing disease. The colonisation period, shedding and exploratory immunology will be assessed during a 17-day inpatient stay and follow-up over 1 year. The dose of inoculum that achieves 70% colonisation will then be confirmed in phase B, comparing healthy participants exposed to B. pertussis with a control group receiving a sham inoculum.Ethics and disseminationThis study has been approved by the ethical committee reference: 17/SC/0006, 24 February 2017. Findings will be published in peer-reviewed open access journals as soon as possible.