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

Investigating Bordetella pertussis colonisation and immunity: protocol for an inpatient controlled human infection model
Investigating Bordetella pertussis colonisation and immunity: protocol for an inpatient controlled human infection model
Introduction: We 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 analysis: A 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 dissemination: This 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.
Journal Article
2044-6055
e018594
De Graaf, Hans
447e78ed-346f-45bb-9238-fce2118d5559
Gbesemete, Diane F.
17afda02-c7ee-4711-9c1e-8ced94a77fd5
Gorringe, Andrew R.
00257a3d-0c2b-479b-ab37-c7b7f65445a3
Diavatopoulos, Dimitri A.
affbc396-d2f3-4edf-8907-04db507b01fd
Kester, Kent E.
dbd7d6c7-9cbd-4ce6-b628-200b9671ed43
Faust, Saul N.
f97df780-9f9b-418e-b349-7adf63e150c1
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
De Graaf, Hans
447e78ed-346f-45bb-9238-fce2118d5559
Gbesemete, Diane F.
17afda02-c7ee-4711-9c1e-8ced94a77fd5
Gorringe, Andrew R.
00257a3d-0c2b-479b-ab37-c7b7f65445a3
Diavatopoulos, Dimitri A.
affbc396-d2f3-4edf-8907-04db507b01fd
Kester, Kent E.
dbd7d6c7-9cbd-4ce6-b628-200b9671ed43
Faust, Saul N.
f97df780-9f9b-418e-b349-7adf63e150c1
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51

De Graaf, Hans, Gbesemete, Diane F., Gorringe, Andrew R., Diavatopoulos, Dimitri A., Kester, Kent E., Faust, Saul N. and Read, Robert C. (2017) Investigating Bordetella pertussis colonisation and immunity: protocol for an inpatient controlled human infection model. BMJ Open, 7 (10), e018594. (doi:10.1136/bmjopen-2017-018594).

Record type: Article

Abstract

Introduction: We 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 analysis: A 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 dissemination: This 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.

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Bp human challenge protocol phase A BMJOpen - Version of Record
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More information

Accepted/In Press date: 11 September 2017
e-pub ahead of print date: 11 October 2017
Published date: October 2017
Additional Information: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Keywords: Journal Article

Identifiers

Local EPrints ID: 417136
URI: https://eprints.soton.ac.uk/id/eprint/417136
ISSN: 2044-6055
PURE UUID: e88fe6de-9c54-43c5-9d7e-e7a8cd6e77d4
ORCID for Saul N. Faust: ORCID iD orcid.org/0000-0003-3410-7642
ORCID for Robert C. Read: ORCID iD orcid.org/0000-0002-4297-6728

Catalogue record

Date deposited: 19 Jan 2018 17:30
Last modified: 10 Dec 2019 01:43

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