# Controlled Human Infection of Healthy Adults With Lyophilized Neisseria lactamica Induces Asymptomatic, Immunogenic Nasopharyngeal Carriage in the United Kingdom and Mali

## TL;DR

A harmless bacteria, Neisseria lactamica, can safely colonize the nose of healthy adults and boost immune responses against meningitis-causing bacteria.

## Contribution

Demonstrates that lyophilized Neisseria lactamica can safely induce colonization and immune responses in two distinct populations.

## Key findings

- Intranasal LyoNlac was well tolerated with no significant safety concerns.
- LyoNlac induced immunogenic colonization in healthy adults in both the UK and Mali.
- Colonized participants showed increased Nlac- and Nmen-specific IgG levels.

## Abstract

Carriage of Neisseria lactamica (Nlac), a harmless nasopharyngeal commensal, correlates inversely with carriage of Neisseria meningitidis (Nmen), a common cause of meningitis and sepsis outbreaks in sub-Saharan Africa. Nasally administered lyophilized Nlac (LyoNlac) might interrupt carriage and transmission of Nmen in sub-Saharan settings without requirement of a cold chain, but whether LyoNlac can establish colonization is undetermined.

Healthy adult volunteers aged 18–45 years were inoculated intranasally with 104–107 colony forming units (CFU) of reconstituted, lyophilized Nlac strain Y92-1009 (LyoNlac) in 2 dose-ranging controlled human infection studies conducted in the United Kingdom and Mali. Safety was measured as a primary objective. Secondary objectives included the dose achieving ≥70% colonization rates for each setting, colonization kinetics, and serological responses. Both trials were registered with ClinicalTrials.gov (United Kingdom: NCT04135053, Mali: NCT04665791) and are complete.

Intranasal inoculation with LyoNlac was well tolerated with no significant safety concerns. In the United Kingdom, 105 CFU yielded 100% colonization (n = 10/10) while in Mali, 107 CFU achieved 65% colonization (n = 13/20). An increase in Nlac- and Nmen-specific IgG from pre-challenge to day 28 post-challenge was observed in colonized participants—median fold-change [interquartile range] United Kingdom: Nlac 2.24 [1.37–4.24], Nmen 1.39 [1.20–3.70] and Mali: Nlac 1.31 [1.04–1.94], Nmen 1.32 [0.99–1.73]. No significant seroconversion occurred in non-colonized participants.

Intranasal inoculation with LyoNlac was safe and induced immunogenic nasopharyngeal colonization in healthy adults in the United Kingdom and Mali. Future clinical trials to determine whether LyoNlac reduces meningococcal carriage and transmission in the meningitis belt are warranted.

Controlled human infection with a lyophilized preparation of the harmless commensal Neisseria lactamica induces safe nasopharyngeal colonization in healthy adults in the United Kingdom and Mali, which induces Neisseria lactamica-specific and cross-reactive Neisseria meningitidis-specific immune responses.