Introduction Neisseria lactamica is a commensal organism found in the human nasopharynx and is closely related to the pathogen N. meningitidis (meningococcus). Carriage of N. lactamica is associated with reduced meningococcal carriage and disease. We summarise an ethically approved protocol for an experimental human challenge study using a genetically modified strain of N. lactamica that expresses the meningococcal antigen NadA. We aim to develop a model to study the role of specific bacterial antigens in nasopharyngeal carriage and immunity, to evaluate vaccines for their efficacy in preventing colonisation and to provide a proof of principle for the development of bacterial medicines. Methods and analysis Healthy adult volunteers aged 18-45 years will receive an intranasal inoculation of either the NadA containing strain of N. lactamica or a genetically modified, but wild-type equivalent control strain. These challenge volunteers will be admitted for 4.5 days observation following inoculation and will then be discharged with strict infection control rules. Bedroom contacts of the challenge volunteers will also be enrolled as contact volunteers. Safety, colonisation, shedding, transmission and immunogenicity will be assessed over 90 days after which carriage will be terminated with antibiotic eradication therapy. Ethics and dissemination This study has been approved by the Department for Environment, Food and Rural Affairs and South Central Oxford A Research Ethics Committee (reference: 18/SC/0133). Findings will be published in peer-reviewed open-access journals as soon as possible. Trial registration number NCT03630250; Pre-results.
Bibliographical noteFunding Information:
MR/N026993/1) 'Pathfinder: Experimental Human Challenge with Genetically Modified Commensals to Investigate Respiratory Tract Mucosal Immunity and Colonisation' and the MRC Confidence in Concept Award, with additional funding from Experimental Medicine by the National Institute for Health Research through support from the Southampton NIHR CRF and the Biomedical Research Centre. The development of the technology underpinning the genetic modification was funded by the Medical Research Council (a genetically modified nasopharyngeal commensal as a platform for bacterial therapy, MR/N013204/1).
Funding This work will be supported by the Medical Research Council (Grant
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
- Genetically modified organism
- Human challenge study
- Neisseria lactamica