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Controlled human infection with Bordetella pertussis induces asymptomatic, immunising colonisation

Controlled human infection with Bordetella pertussis induces asymptomatic, immunising colonisation
Controlled human infection with Bordetella pertussis induces asymptomatic, immunising colonisation
Background
Bordetella pertussis is among the leading causes of vaccine-preventable deaths and morbidity globally. Human asymptomatic carriage as a reservoir for community transmission of infections might be a target of future vaccine strategies, but has not been demonstrated. Our objective was to demonstrate that asymptomatic nasopharyngeal carriage of Bordetella pertussis is inducible in humans and to define the microbiological and immunological features of presymptomatic infection.Methods
Healthy subjects aged 18–45 years with an antipertussis toxin immunoglobin G (IgG) concentration of <20 international units/ml were inoculated intranasally with nonattenuated, wild-type Bordetella pertussis strain B1917. Safety, colonization, and shedding were monitored over 17 days in an inpatient facility. Colonization was assessed by culture and quantitative polymerase chain reaction. Azithromycin was administered from Day 14. The inoculum dose was escalated, aiming to colonize at least 70% of participants. Immunological responses were measured.
Results
There were 34 participants challenged, in groups of 4 or 5. The dose was gradually escalated from 103 colony-forming units (0% colonized) to 105 colony-forming units (80% colonized). Minor symptoms were reported in a minority of participants. Azithromycin eradicated colonization in 48 hours in 88% of colonized individuals. Antipertussis toxin IgG seroconversion occurred in 9 out of 19 colonized participants and in none of the participants who were not colonized. Nasal wash was a more sensitive method to detect colonization than pernasal swabs. No shedding of Bordetella pertussis was detected in systematically collected environmental samples.
Conclusions
Bordetella pertussis colonization can be deliberately induced and leads to a systemic immune response without causing pertussis symptoms.
Clinical Trials Registration NCT03751514.
1058-4838
403-411
de Graaf, Hans
fb174fd4-5130-4a17-88ca-832c150e94e7
Ibrahim, Muktar
92069adb-ce7d-4cb1-9491-c1c68bb5be19
Hill, Alison R
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Gbesemete, Diane
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Vaughan, Andrew T
bfb2ceab-a592-457e-89f9-00fcd1dddbdb
Gorringe, Andrew
503cb828-4e75-44e9-a8af-61f814e02bc6
Preston, Andrew
f8d06589-7c45-4286-9abd-fc805bff2039
Buisman, Annemaire M
f182b980-b998-4417-b720-78c2a3e039a3
Faust, Saul
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Kester, Kent E.
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Berbers, Guy
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Diavatopoulos, Dimitri A.
affbc396-d2f3-4edf-8907-04db507b01fd
Read, Robert
b5caca7b-0063-438a-b703-7ecbb6fc2b51
de Graaf, Hans
fb174fd4-5130-4a17-88ca-832c150e94e7
Ibrahim, Muktar
92069adb-ce7d-4cb1-9491-c1c68bb5be19
Hill, Alison R
de7a9d4f-7c5c-440c-9619-5b390f6347fd
Gbesemete, Diane
45c5ae20-20f8-4bc0-b3cd-c9a102e94471
Vaughan, Andrew T
bfb2ceab-a592-457e-89f9-00fcd1dddbdb
Gorringe, Andrew
503cb828-4e75-44e9-a8af-61f814e02bc6
Preston, Andrew
f8d06589-7c45-4286-9abd-fc805bff2039
Buisman, Annemaire M
f182b980-b998-4417-b720-78c2a3e039a3
Faust, Saul
f97df780-9f9b-418e-b349-7adf63e150c1
Kester, Kent E.
dbd7d6c7-9cbd-4ce6-b628-200b9671ed43
Berbers, Guy
b75f6de3-9c7f-41bf-94ba-8ae0c5259829
Diavatopoulos, Dimitri A.
affbc396-d2f3-4edf-8907-04db507b01fd
Read, Robert
b5caca7b-0063-438a-b703-7ecbb6fc2b51

de Graaf, Hans, Ibrahim, Muktar, Hill, Alison R, Gbesemete, Diane, Vaughan, Andrew T, Gorringe, Andrew, Preston, Andrew, Buisman, Annemaire M, Faust, Saul, Kester, Kent E., Berbers, Guy, Diavatopoulos, Dimitri A. and Read, Robert (2020) Controlled human infection with Bordetella pertussis induces asymptomatic, immunising colonisation. Clinical Infectious Diseases, 71 (2), 403-411. (doi:10.1093/cid/ciz840).

Record type: Article

Abstract

Background
Bordetella pertussis is among the leading causes of vaccine-preventable deaths and morbidity globally. Human asymptomatic carriage as a reservoir for community transmission of infections might be a target of future vaccine strategies, but has not been demonstrated. Our objective was to demonstrate that asymptomatic nasopharyngeal carriage of Bordetella pertussis is inducible in humans and to define the microbiological and immunological features of presymptomatic infection.Methods
Healthy subjects aged 18–45 years with an antipertussis toxin immunoglobin G (IgG) concentration of <20 international units/ml were inoculated intranasally with nonattenuated, wild-type Bordetella pertussis strain B1917. Safety, colonization, and shedding were monitored over 17 days in an inpatient facility. Colonization was assessed by culture and quantitative polymerase chain reaction. Azithromycin was administered from Day 14. The inoculum dose was escalated, aiming to colonize at least 70% of participants. Immunological responses were measured.
Results
There were 34 participants challenged, in groups of 4 or 5. The dose was gradually escalated from 103 colony-forming units (0% colonized) to 105 colony-forming units (80% colonized). Minor symptoms were reported in a minority of participants. Azithromycin eradicated colonization in 48 hours in 88% of colonized individuals. Antipertussis toxin IgG seroconversion occurred in 9 out of 19 colonized participants and in none of the participants who were not colonized. Nasal wash was a more sensitive method to detect colonization than pernasal swabs. No shedding of Bordetella pertussis was detected in systematically collected environmental samples.
Conclusions
Bordetella pertussis colonization can be deliberately induced and leads to a systemic immune response without causing pertussis symptoms.
Clinical Trials Registration NCT03751514.

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Accepted/In Press date: 22 August 2019
e-pub ahead of print date: 28 September 2019
Published date: 15 July 2020

Identifiers

Local EPrints ID: 434733
URI: http://eprints.soton.ac.uk/id/eprint/434733
ISSN: 1058-4838
PURE UUID: a6d38ffc-8921-4210-9b4b-000ad26e4448
ORCID for Alison R Hill: ORCID iD orcid.org/0000-0001-5397-873X
ORCID for Andrew T Vaughan: ORCID iD orcid.org/0000-0001-6076-3649
ORCID for Saul Faust: ORCID iD orcid.org/0000-0003-3410-7642
ORCID for Robert Read: ORCID iD orcid.org/0000-0002-4297-6728

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Date deposited: 07 Oct 2019 16:31
Last modified: 15 Sep 2021 05:23

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