Protocol for a controlled human infection with genetically modified Neisseria lactamica expressing the meningococcal vaccine antigens NadA and FHbp: The GM-Nlac Pilot Study
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Introduction
Previous work has shown that experimentally induced colonisation with Neisseria lactamica (Nlac) is safe and associated with reduced meningococcal colonisation. This pilot study aims to establish the safety, induction of colonisation and immunogenicity following intranasal inoculation with a mixture of four strains of genetically modified Nlac (GM-Nlac). Each of these strains express meningococcal vaccine antigens present in current vaccines: Neisseria adhesin A (NadA) and one of four different variants of Factor H-binding protein (FHbp), the latter of which is specifically mutated to abrogate its ability to bind the human complement protein, Factor H.
Methods and analysis
In this controlled human infection model experiment, 10 healthy participants aged 18-45 years will be inoculated with a mixture of 4 strains of GM-Nlac (collectively referred to as the challenge agent, 4xrNlac). They will be followed up over 28 days to assess colonisation, immunogenicity and efficacy of eradication with a single oral dose of ciprofloxacin (500 mg). Participant contacts will also be recruited to assess for onward transmission of GM-Nlac.
Ethics and dissemination
This study involves the deliberate release of four genetically modified organisms, which has been approved by the Department for Environment, Food and Rural Affairs (reference: 25/R50/01). The clinical study has also been approved by South-Central Oxford A Research Ethics Committee and the Health Research Authority (reference: 26/SC/0072). All participants will provide written informed consent prior to enrolment. Findings of the study will be submitted for publication in a peer-reviewed scientific journal and for presentation at scientific conferences.
Registration
This study is registered on the ISRCTN registry with study registration number ISRCTN10930766
Strength and limitations of the study
Strengths
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A platform controlled human infection model that will enable the study of human mucosal immune responses to single gene products of Neisseria meningitidis .
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A pathfinder study that will guide potential future mucosal immunoprophylaxis.
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Rigorous protocol for safety evaluation of a deliberately released multistrain genetically modified live bacterial product.
Limitations
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Small exploratory pilot study.
