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.
Bibliographical noteFunding 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.
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.
© 2015 The Author.
- Neisseria lactamica
- Neisseria meningitidis
- herd protection
- meningococcal carriage
- meningococcal vaccination