Controlled human infection with <i>Neisseria lactamica</i> in late pregnancy to measure horizontal transmission and microbiome changes in mother-neonate pairs: a single-arm interventional pilot study protocol.

Abstract

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. <i>Neisseria lactamica</i> is a common pharyngeal commensal in young children and is associated with reduced carriage and invasive disease by <i>Neisseria meningitidis</i>. Nasal inoculation with <i>N. lactamica</i> safely and reproducibly reduces <i>N. meningitidis</i> colonisation in healthy adults. We propose nasal inoculation of pregnant women with <i>N. lactamica</i>, to establish if neonatal pharyngeal colonisation occurs after birth, and to characterise microbiome evolution in mother-infant pairs over 1 month post partum. 20 healthy pregnant women will receive nasal inoculation with <i>N. lactamica</i> (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, <i>N. lactamica</i> colonisation (by targeted PCR) and longitudinal microevolution (by whole genome sequencing), and microbiome evolution (by 16S rRNA gene sequencing). 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. NCT04784845.