Controlled human infection with Neisseria lactamica in late pregnancy to measure horizontal transmission and microbiome changes in mother-neonate pairs: A single-arm interventional pilot study protocol
Controlled human infection with Neisseria lactamica in late pregnancy to measure horizontal transmission and microbiome changes in mother-neonate pairs: A single-arm interventional pilot study protocol
INTRODUCTION: Infant upper respiratory microbiota are derived partly from the maternal respiratory tract, and certain microbiota are associated with altered risk of infections and respiratory disease. Neisseria lactamica is a common pharyngeal commensal in young children and is associated with reduced carriage and invasive disease by Neisseria meningitidis. Nasal inoculation with N. lactamica safely and reproducibly reduces N. meningitidis colonisation in healthy adults. We propose nasal inoculation of pregnant women with N. lactamica, to establish if neonatal pharyngeal colonisation occurs after birth, and to characterise microbiome evolution in mother-infant pairs over 1 month post partum.
METHODS AND ANALYSIS: 20 healthy pregnant women will receive nasal inoculation with N. lactamica (wild type strain Y92-1009) at 36-38 weeks gestation. Upper respiratory samples, as well as optional breastmilk, umbilical cord blood and infant venous blood samples, will be collected from mother-infant pairs over 1 month post partum. We will assess safety, N. lactamica colonisation (by targeted PCR) and longitudinal microevolution (by whole genome sequencing), and microbiome evolution (by 16S rRNA gene sequencing).
ETHICS AND DISSEMINATION: This study has been approved by the London Central Research Ethics Committee (21/PR/0373). Findings will be published in peer-reviewed open-access journals as soon as possible.TRIAL REGISTRATION NUMBER: NCT04784845.
Adult, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Microbiota/genetics, Mothers, Neisseria lactamica/genetics, Neisseria meningitidis, Pharynx, Pilot Projects, Pregnancy, RNA, Ribosomal, 16S
Theodosiou, Anastasia A
c6e63581-c22d-4a2c-9d14-2e66594eb053
Laver, Jay R
b2996398-2ccf-40f0-92b8-f338f3de796b
Dale, Adam P
5096a630-1d0b-4e37-a1d4-e971e08acb54
Cleary, David W
f4079c6d-d54b-4108-b346-b0069035bec0
Jones, Christine E
48229079-8b58-4dcb-8374-d9481fe7b426
Read, Robert C
b5caca7b-0063-438a-b703-7ecbb6fc2b51
18 May 2022
Theodosiou, Anastasia A
c6e63581-c22d-4a2c-9d14-2e66594eb053
Laver, Jay R
b2996398-2ccf-40f0-92b8-f338f3de796b
Dale, Adam P
5096a630-1d0b-4e37-a1d4-e971e08acb54
Cleary, David W
f4079c6d-d54b-4108-b346-b0069035bec0
Jones, Christine E
48229079-8b58-4dcb-8374-d9481fe7b426
Read, Robert C
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Theodosiou, Anastasia A, Laver, Jay R, Dale, Adam P, Cleary, David W, Jones, Christine E and Read, Robert C
(2022)
Controlled human infection with Neisseria lactamica in late pregnancy to measure horizontal transmission and microbiome changes in mother-neonate pairs: A single-arm interventional pilot study protocol.
BMJ Open, 12 (5), [e056081].
(doi:10.1136/bmjopen-2021-056081).
Abstract
INTRODUCTION: Infant upper respiratory microbiota are derived partly from the maternal respiratory tract, and certain microbiota are associated with altered risk of infections and respiratory disease. Neisseria lactamica is a common pharyngeal commensal in young children and is associated with reduced carriage and invasive disease by Neisseria meningitidis. Nasal inoculation with N. lactamica safely and reproducibly reduces N. meningitidis colonisation in healthy adults. We propose nasal inoculation of pregnant women with N. lactamica, to establish if neonatal pharyngeal colonisation occurs after birth, and to characterise microbiome evolution in mother-infant pairs over 1 month post partum.
METHODS AND ANALYSIS: 20 healthy pregnant women will receive nasal inoculation with N. lactamica (wild type strain Y92-1009) at 36-38 weeks gestation. Upper respiratory samples, as well as optional breastmilk, umbilical cord blood and infant venous blood samples, will be collected from mother-infant pairs over 1 month post partum. We will assess safety, N. lactamica colonisation (by targeted PCR) and longitudinal microevolution (by whole genome sequencing), and microbiome evolution (by 16S rRNA gene sequencing).
ETHICS AND DISSEMINATION: This study has been approved by the London Central Research Ethics Committee (21/PR/0373). Findings will be published in peer-reviewed open-access journals as soon as possible.TRIAL REGISTRATION NUMBER: NCT04784845.
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e056081.full
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Accepted/In Press date: 30 April 2022
e-pub ahead of print date: 18 May 2022
Published date: 18 May 2022
Additional Information:
Funding Information:
This work is supported by a Medical Research Council Clinical Research Training Fellowship (grant number MR/V002015/1) awarded to AAT. RCR is an NIHR Senior Investigator. The funders have not had input into the design or execution of the study or the preparation of this manuscript.
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
Keywords:
Adult, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Microbiota/genetics, Mothers, Neisseria lactamica/genetics, Neisseria meningitidis, Pharynx, Pilot Projects, Pregnancy, RNA, Ribosomal, 16S
Identifiers
Local EPrints ID: 457513
URI: http://eprints.soton.ac.uk/id/eprint/457513
ISSN: 2044-6055
PURE UUID: ddfaefc4-1075-4706-ab38-ab5327eb5fd9
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Date deposited: 09 Jun 2022 17:33
Last modified: 11 Dec 2024 03:03
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Author:
Anastasia A Theodosiou
Author:
Adam P Dale
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