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

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.