title: Nasal Inoculation of the Commensal Neisseria lactamica Inhibits Carriage of Neisseria meningitidis by Young Adults: A Controlled Human Infection Study.
abstract: 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 10(4) 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.
  
  
  BACKGROUND
  NCT02249598.
authors: Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals Foundation Trust.
authors: Alice M
authors: AM
authors: Deasy
authors: Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals Foundation Trust.
authors: Ed
authors: E
authors: Guccione
authors: Academic Unit of Clinical and Experimental Sciences and Institute for Life Sciences, University of Southampton, and NIHR Respiratory Biomedical Research Unit, University Hospital Southampton.
authors: Adam P
authors: AP
authors: Dale
authors: Statistics, Modeling and Economics Department, Health Protection Directorate, Public Health England, London.
authors: Nick
authors: N
authors: Andrews
authors: Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals Foundation Trust.
authors: Cariad M
authors: CM
authors: Evans
authors: Department of Zoology, University of Oxford.
authors: Julia S
authors: JS
authors: Bennett
authors: Department of Zoology, University of Oxford.
authors: Holly B
authors: HB
authors: Bratcher
authors: Department of Zoology, University of Oxford.
authors: Martin C J
authors: MC
authors: Maiden
authors: Public Health England, Porton Down, Salisbury, United Kingdom.
authors: Andrew R
authors: AR
authors: Gorringe
authors: Academic Unit of Clinical and Experimental Sciences and Institute for Life Sciences, University of Southampton, and NIHR Respiratory Biomedical Research Unit, University Hospital Southampton.
authors: Robert C
authors: RC
authors: Read
mesh_terms: D000293:Adolescent; D000328:Adult; D000898:Antibiosis; D002353:Carrier State / Q000382:microbiology* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D008589:Meningococcal Infections / Q000382:microbiology* / Q000517:prevention & control*; D042806:Neisseria lactamica / Q000254:growth & development*; D009345:Neisseria meningitidis / Q000302:isolation & purification*; D019936:Probiotics / Q000008:administration & dosage*; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
keywords: Neisseria lactamica; Neisseria meningitidis; herd protection; meningococcal carriage; meningococcal vaccination