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Nasal Inoculation of the commensal Neisseria lactamica inhibits carriage of Neisseria meningitidis by young adults: A controlled human infection study

Nasal Inoculation of the commensal Neisseria lactamica inhibits carriage of Neisseria meningitidis by young adults: A controlled human infection study
Nasal Inoculation of the commensal Neisseria lactamica inhibits carriage of Neisseria meningitidis by young adults: A controlled human infection study

BACKGROUND: Herd protection by meningococcal vaccines is conferred by population-level reduction of meningococcal nasopharyngeal colonization. Given the inverse epidemiological association between colonization by commensal Neisseria lactamica and meningococcal disease, we investigated whether controlled infection of human volunteers with N. lactamica prevents colonization by Neisseria meningitidis.

METHODS: In a block-randomized human challenge study, 310 university students were inoculated with 10(4) colony-forming units of N. lactamica or were sham-inoculated, and carriage was monitored for 26 weeks, after which all participants were reinoculated with N. lactamica and resampled 2 weeks later.

RESULTS: At baseline, natural N. meningitidis carriage in the control group was 22.4% (36/161), which increased to 33.6% (48/143) by week 26. Two weeks after inoculation of N. lactamica, 33.6% (48/143) of the challenge group became colonized with N. lactamica. In this group, meningococcal carriage reduced from 24.2% (36/149) at inoculation to 14.7% (21/143) 2 weeks after inoculation (-9.5%; P = .006). The inhibition of meningococcal carriage was only observed in carriers of N. lactamica, was due both to displacement of existing meningococci and to inhibition of new acquisition, and persisted over at least 16 weeks. Crossover inoculation of controls with N. lactamica replicated the result. Genome sequencing showed that inhibition affected multiple meningococcal sequence types.

CONCLUSIONS: The inhibition of meningococcal carriage by N. lactamica is even more potent than after glycoconjugate meningococcal vaccination. Neisseria lactamica or its components could be a novel bacterial medicine to suppress meningococcal outbreaks. This observation explains the epidemiological observation of natural immunity conferred by carriage of N. lactamica.

CLINICAL TRIALS REGISTRATION: NCT02249598.

Adolescent, Adult, Antibiosis, Carrier State, Female, Humans, Male, Meningococcal Infections, Neisseria lactamica, Neisseria meningitidis, Probiotics, Prospective Studies, Treatment Outcome, Young Adult, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
1058-4838
1512-1520
Deasy, Alice M.
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Guccione, Ed
9601785b-dd62-441e-b09f-24502a347f40
Dale, Adam P.
5096a630-1d0b-4e37-a1d4-e971e08acb54
Andrews, Nick
7d63cec1-f343-4e37-83b3-8f80e4022ed4
Evans, Cariad M.
fae80ca3-76d3-4c99-8407-dca44389c83f
Bennett, Julia S.
b7bfe6e4-7538-424f-932d-8499fb7e8180
Bratcher, Holly B.
9f9e785a-44ef-4d44-a4ee-e534bdae053e
Maiden, Martin C.J.
721886a4-7548-45c8-882f-7a9cae695c0c
Gorringe, Andrew R.
00257a3d-0c2b-479b-ab37-c7b7f65445a3
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Deasy, Alice M.
fb26eee8-b009-49e5-ac45-6c1ab92b837f
Guccione, Ed
9601785b-dd62-441e-b09f-24502a347f40
Dale, Adam P.
5096a630-1d0b-4e37-a1d4-e971e08acb54
Andrews, Nick
7d63cec1-f343-4e37-83b3-8f80e4022ed4
Evans, Cariad M.
fae80ca3-76d3-4c99-8407-dca44389c83f
Bennett, Julia S.
b7bfe6e4-7538-424f-932d-8499fb7e8180
Bratcher, Holly B.
9f9e785a-44ef-4d44-a4ee-e534bdae053e
Maiden, Martin C.J.
721886a4-7548-45c8-882f-7a9cae695c0c
Gorringe, Andrew R.
00257a3d-0c2b-479b-ab37-c7b7f65445a3
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51

Deasy, Alice M., Guccione, Ed, Dale, Adam P., Andrews, Nick, Evans, Cariad M., Bennett, Julia S., Bratcher, Holly B., Maiden, Martin C.J., Gorringe, Andrew R. and Read, Robert C. (2015) Nasal Inoculation of the commensal Neisseria lactamica inhibits carriage of Neisseria meningitidis by young adults: A controlled human infection study. Clinical Infectious Diseases, 60 (10), 1512-1520. (doi:10.1093/cid/civ098).

Record type: Article

Abstract

BACKGROUND: Herd protection by meningococcal vaccines is conferred by population-level reduction of meningococcal nasopharyngeal colonization. Given the inverse epidemiological association between colonization by commensal Neisseria lactamica and meningococcal disease, we investigated whether controlled infection of human volunteers with N. lactamica prevents colonization by Neisseria meningitidis.

METHODS: In a block-randomized human challenge study, 310 university students were inoculated with 10(4) colony-forming units of N. lactamica or were sham-inoculated, and carriage was monitored for 26 weeks, after which all participants were reinoculated with N. lactamica and resampled 2 weeks later.

RESULTS: At baseline, natural N. meningitidis carriage in the control group was 22.4% (36/161), which increased to 33.6% (48/143) by week 26. Two weeks after inoculation of N. lactamica, 33.6% (48/143) of the challenge group became colonized with N. lactamica. In this group, meningococcal carriage reduced from 24.2% (36/149) at inoculation to 14.7% (21/143) 2 weeks after inoculation (-9.5%; P = .006). The inhibition of meningococcal carriage was only observed in carriers of N. lactamica, was due both to displacement of existing meningococci and to inhibition of new acquisition, and persisted over at least 16 weeks. Crossover inoculation of controls with N. lactamica replicated the result. Genome sequencing showed that inhibition affected multiple meningococcal sequence types.

CONCLUSIONS: The inhibition of meningococcal carriage by N. lactamica is even more potent than after glycoconjugate meningococcal vaccination. Neisseria lactamica or its components could be a novel bacterial medicine to suppress meningococcal outbreaks. This observation explains the epidemiological observation of natural immunity conferred by carriage of N. lactamica.

CLINICAL TRIALS REGISTRATION: NCT02249598.

Full text not available from this repository.

More information

Accepted/In Press date: 2 February 2015
e-pub ahead of print date: 28 April 2015
Published date: 15 May 2015
Additional Information: © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Keywords: Adolescent, Adult, Antibiosis, Carrier State, Female, Humans, Male, Meningococcal Infections, Neisseria lactamica, Neisseria meningitidis, Probiotics, Prospective Studies, Treatment Outcome, Young Adult, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 418310
URI: https://eprints.soton.ac.uk/id/eprint/418310
ISSN: 1058-4838
PURE UUID: 99bb90eb-f5c6-4531-bf15-ff36faf44f81
ORCID for Adam P. Dale: ORCID iD orcid.org/0000-0001-8163-7481
ORCID for Robert C. Read: ORCID iD orcid.org/0000-0002-4297-6728

Catalogue record

Date deposited: 27 Feb 2018 17:32
Last modified: 14 Mar 2019 01:36

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Contributors

Author: Alice M. Deasy
Author: Ed Guccione
Author: Adam P. Dale ORCID iD
Author: Nick Andrews
Author: Cariad M. Evans
Author: Julia S. Bennett
Author: Holly B. Bratcher
Author: Martin C.J. Maiden
Author: Andrew R. Gorringe
Author: Robert C. Read ORCID iD

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