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

Alice M. Deasy; Ed Guccione; Adam P. Dale; Nicholas Andrews; Cariad M. Evans; Julia S. Bennett; Holly B. Bratcher; Martin C.J. Maiden; Andrew Gorringe; Robert C. Read

doi:10.1093/cid/civ098

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

Alice M. Deasy, Ed Guccione, Adam P. Dale, Nicholas Andrews, Cariad M. Evans, Julia S. Bennett, Holly B. Bratcher, Martin C.J. Maiden, Andrew Gorringe, Robert C. Read^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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 10⁴ 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.

Original language	English
Pages (from-to)	1512-1520
Number of pages	9
Journal	Clinical Infectious Diseases
Volume	60
Issue number	10
DOIs	https://doi.org/10.1093/cid/civ098
Publication status	Published - 15 May 2015

Bibliographical note

Funding Information:
Financial support. This work was supported by Life for a Cure, a charity established by Michelle and John Bresnahan in memory of their son Ryan; and Meningitis UK (now Meningitis Now). Potential conflicts of interest. All authors: No reported conflicts.

Funding Information:
Acknowledgments. Infrastructure and Service support was provided by the National Institute of Health Research Clinical Research Network, UK. We are grateful to the university volunteers who took part in this project and would also like to thank Abida Nazir and the staff in the Clinical Research Unit at the Royal Hallamshire Hospital, Sheffield, UK for their help with patient recruitment and support in the clinical work. In addition we thank Ian Geary, Marika Sazbo, Robert Ridley, Ben Harvey, Laura Harrison, Richard Jones, and Risat Ul Haque for laboratory support.

Publisher Copyright:
© 2015 The Author.

Keywords

Neisseria lactamica
Neisseria meningitidis
herd protection
meningococcal carriage
meningococcal vaccination

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/cid/civ098

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Deasy, A. M., Guccione, E., Dale, A. P., Andrews, N., Evans, C. M., Bennett, J. S., Bratcher, H. B., Maiden, M. C. J., Gorringe, A., & Read, R. 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. https://doi.org/10.1093/cid/civ098

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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 104 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.",

keywords = "Neisseria lactamica, Neisseria meningitidis, herd protection, meningococcal carriage, meningococcal vaccination",

author = "Deasy, {Alice M.} and Ed Guccione and Dale, {Adam P.} and Nicholas Andrews and Evans, {Cariad M.} and Bennett, {Julia S.} and Bratcher, {Holly B.} and Maiden, {Martin C.J.} and Andrew Gorringe and Read, {Robert C.}",

note = "Funding Information: Financial support. This work was supported by Life for a Cure, a charity established by Michelle and John Bresnahan in memory of their son Ryan; and Meningitis UK (now Meningitis Now). Potential conflicts of interest. All authors: No reported conflicts. Funding Information: Acknowledgments. Infrastructure and Service support was provided by the National Institute of Health Research Clinical Research Network, UK. We are grateful to the university volunteers who took part in this project and would also like to thank Abida Nazir and the staff in the Clinical Research Unit at the Royal Hallamshire Hospital, Sheffield, UK for their help with patient recruitment and support in the clinical work. In addition we thank Ian Geary, Marika Sazbo, Robert Ridley, Ben Harvey, Laura Harrison, Richard Jones, and Risat Ul Haque for laboratory support. Publisher Copyright: {\textcopyright} 2015 The Author.",

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month = may,

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doi = "10.1093/cid/civ098",

language = "English",

volume = "60",

pages = "1512--1520",

journal = "Clinical Infectious Diseases",

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Deasy, AM, Guccione, E, Dale, AP, Andrews, N, Evans, CM, Bennett, JS, Bratcher, HB, Maiden, MCJ, Gorringe, A & Read, RC 2015, 'Nasal inoculation of the commensal neisseria lactamica inhibits carriage of neisseria meningitidis by young adults: A controlled human infection study', Clinical Infectious Diseases, vol. 60, no. 10, pp. 1512-1520. https://doi.org/10.1093/cid/civ098

TY - JOUR

T1 - Nasal inoculation of the commensal neisseria lactamica inhibits carriage of neisseria meningitidis by young adults

T2 - A controlled human infection study

AU - Deasy, Alice M.

AU - Guccione, Ed

AU - Dale, Adam P.

AU - Andrews, Nicholas

AU - Evans, Cariad M.

AU - Bennett, Julia S.

AU - Bratcher, Holly B.

AU - Maiden, Martin C.J.

AU - Gorringe, Andrew

AU - Read, Robert C.

N1 - Funding Information: Financial support. This work was supported by Life for a Cure, a charity established by Michelle and John Bresnahan in memory of their son Ryan; and Meningitis UK (now Meningitis Now). Potential conflicts of interest. All authors: No reported conflicts. Funding Information: Acknowledgments. Infrastructure and Service support was provided by the National Institute of Health Research Clinical Research Network, UK. We are grateful to the university volunteers who took part in this project and would also like to thank Abida Nazir and the staff in the Clinical Research Unit at the Royal Hallamshire Hospital, Sheffield, UK for their help with patient recruitment and support in the clinical work. In addition we thank Ian Geary, Marika Sazbo, Robert Ridley, Ben Harvey, Laura Harrison, Richard Jones, and Risat Ul Haque for laboratory support. Publisher Copyright: © 2015 The Author.

PY - 2015/5/15

Y1 - 2015/5/15

N2 - 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 104 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.

AB - 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 104 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.

KW - Neisseria lactamica

KW - Neisseria meningitidis

KW - herd protection

KW - meningococcal carriage

KW - meningococcal vaccination

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U2 - 10.1093/cid/civ098

DO - 10.1093/cid/civ098

M3 - Article

C2 - 25814628

AN - SCOPUS:84929179287

SN - 1058-4838

VL - 60

SP - 1512

EP - 1520

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 10

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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