title: Development and characterisation of outer membrane vesicle vaccines against serogroup A Neisseria meningitidis.
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.
authors.affiliation: Division of Infectious Disease Control, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, NO-0403 Oslo, Norway.
authors.forename: Gunnstein
authors.initials: G
authors.lastname: Norheim
authors.forename: Audun
authors.initials: A
authors.lastname: Aase
authors.forename: Dominique A
authors.initials: DA
authors.lastname: Caugant
authors.forename: E Arne
authors.initials: EA
authors.lastname: Høiby
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Fritzsønn
authors.forename: Torill
authors.initials: T
authors.lastname: Tangen
authors.forename: Paul
authors.initials: P
authors.lastname: Kristiansen
authors.forename: Ulla
authors.initials: U
authors.lastname: Heggelund
authors.forename: Einar
authors.initials: E
authors.lastname: Rosenqvist
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000097:blood; D008070:Lipopolysaccharides / Q000032:analysis; D008585:Meningitis, Meningococcal / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D023421:Models, Animal; D038381:Neisseria meningitidis, Serogroup A / Q000737:chemistry / Q000276:immunology*; D010587:Phagocytosis
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D022401:Meningococcal Vaccines; C023023:lipid-linked oligosaccharides