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Published on: December 8, 2023
Development and characterisation of outer membrane vesicle vaccines against serogroup A Neisseria meningitidis
Gunnstein Norheim1, Audun Aase, Dominique A Caugant
1Division of Infectious Disease Control, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, NO-0403 Oslo, Norway.
Abstract:
Neisseria meningitidis bacteria of serogroup A are causing recurring meningitis epidemics on the African continent. An outer membrane vesicle (OMV) vaccine against serogroup A meningococci made from a subgroup III serogroup A meningococcal strain was previously shown to induce antibodies with serum bactericidal activity (SBA) in mice. We have here further investigated the properties of OMV vaccines made from five different subgroup III serogroup A meningococcal strains grown in a synthetic medium with low iron content. In addition to the major outer membrane proteins (PorA, PorB, RmpM, Opa and OpcA), small amounts of the NadA, TdfH, Omp85, FetA, FbpA and NspA outer membrane proteins, as well as lipooligosaccharides, were detected in the vaccines. The OMV vaccines were used to immunise mice. Anti-meningococcal IgG antibodies in the mouse sera were analysed by immunoblotting and by enzyme-linked immunosorbent assay against OMVs, and against live meningococcal cells in SBA and a flow-cytometric assay. The vaccines induced antibodies with high SBA and opsonophagocytic activity. The strongest IgG responses were directed against PorA. Significant SBA responses were also observed against a subgroup III strain, which did not express PorA, whereas no SBA was observed against a clone IV-1 serogroup A strain. An OMV vaccine from serogroup A meningococci may be an alternative to polysaccharide and conjugate polysaccharide vaccines for Africa.
Insights
Outer membrane vesicle (OMV) vaccines derived from Neisseria meningitidis serogroup A show promise for preventing meningitis epidemics in Africa. These OMV vaccines induce robust immune responses, including high serum bactericidal activity, in mice.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Neisseria meningitidis serogroup A causes recurrent meningitis epidemics in Africa.
- Previous studies showed outer membrane vesicle (OMV) vaccines from subgroup III serogroup A meningococci induced serum bactericidal activity (SBA) in mice.
Purpose of the Study:
- To investigate the properties of OMV vaccines from five different subgroup III serogroup A meningococcal strains.
- To evaluate the immunogenicity and efficacy of these OMV vaccines in a mouse model.
Main Methods:
- OMV vaccines were produced from serogroup A meningococcal strains grown in low-iron synthetic medium.
- Mice were immunized with OMV vaccines, and immune responses were analyzed via immunoblotting, ELISA, serum bactericidal assays (SBA), and flow cytometry.
- Antibody responses were assessed against various outer membrane proteins and lipooligosaccharides.
Main Results:
- OMV vaccines induced antibodies with high SBA and opsonophagocytic activity against Neisseria meningitidis serogroup A.
- The strongest IgG antibody responses were directed against the PorA outer membrane protein.
- Significant SBA was observed against a subgroup III strain lacking PorA, but not against a clone IV-1 strain.
Conclusions:
- OMV vaccines derived from subgroup III serogroup A meningococci are immunogenic and elicit potent bactericidal antibodies in mice.
- These OMV vaccines represent a potential alternative to polysaccharide and conjugate polysaccharide vaccines for controlling serogroup A meningococcal meningitis in Africa.
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