Evaluating expression of meningococcal vaccine targets
Research type
Research Study
Full title
Evaluating expression of meningococcal vaccine targets in clinical samples from meningococcal disease patients
IRAS ID
183919
Contact name
Christopher D Bayliss
Contact email
Sponsor organisation
University of Leicester
Duration of Study in the UK
1 years, 5 months, 31 days
Research summary
This study aims to develop an assay for measuring the RNA or peptides of a specific meningococcal vaccine antigen, fHbp, in clinical samples from meningococcal disease patients. The fHbp protein is one of the major protective antigens contained within Bexsero®, a multicomponent vaccine designed to protect against MenB strains of Neisseria meningitidis (the meningococcus). The amount of fHbp made by a specific meningococcal strains is a critical determinant of whether antibody responses elicited by Bexsero® will protect against that strain. Bexsero® will protect against a meningococcal strain that produces high amounts of fHbp but not low amounts. Bexsero® is predicted to protect against 73-88% of UK meningococcal disease (MD) isolates and hence will not provide universal coverage of MenB strains such that there is a potential for cases of meningococcal disease in vaccinated individuals (i.e. vaccine failures). Determination of whether vaccine failure is due to an infection by a ‘covered-strain’ (i.e. expressing high amounts of fHbp) or a ‘non-covered-strain’ (i.e. expressing low amounts of fHbp) is crucial for assessing the efficacy of the vaccine. Current assays of coverage rely on tests using ‘live’ bacteria while many cases of meningococcal disease are made by PCR-only methods without recovery of the infective strain. We propose to test assays for directly assessing fHbp expression levels in clinical samples in order to determine whether lack of coverage is the cause of vaccine failure. Our primary objective is to determin expression by measuring the amounts of RNA for fHbp in clinical samples from meningococcal disease patients. A mass spectrometry assay will also be tested for measuring amounts of fHbp peptides in clinical samples. A successful assay is needed for routine testing of the efficacy of Bexsero® following introduction of this vaccine into the infant vaccine schedule in September 2015.
REC name
West of Scotland REC 3
REC reference
15/WS/0237
Date of REC Opinion
14 Oct 2015
REC opinion
Favourable Opinion