title: FetA Antibodies Induced by an Outer Membrane Vesicle Vaccine Derived from a Serogroup B Meningococcal Isolate with Constitutive FetA Expression.
abstract: Invasive meningococcal disease causes over 3500 cases each year in Europe, with particularly high incidence among young children. Among serogroup B meningococci, which cause most of the cases, high diversity in the outer membrane proteins (OMPs) is observed in endemic situations; however, comprehensive molecular epidemiological data are available for the diversity and distribution of the OMPs PorA and FetA and these can be used to rationally design a vaccine with high coverage of the case isolates. The aim of this study was to determine whether outer membrane vesicles (OMVs) derived from an isolate with constitutive FetA expression (MenPF-1 vaccine) could be used to induce antibodies against both the PorA and FetA antigens. The immunogenicity of various dose levels and number of doses was evaluated in mice and rabbits, and IgG antibody responses tested against OMVs and recombinant PorA and FetA proteins. A panel of four isogenic mutants was generated and used to evaluate the relative ability of the vaccine to induce serum bactericidal activity (SBA) against FetA and PorA. Sera from mice were tested in SBA against the four target strains. Results demonstrated that the MenPF-1 OMVs were immunogenic against PorA and FetA in both animal models. Furthermore, the murine antibodies induced were bactericidal against isogenic mutant strains, suggesting that antibodies to both PorA and FetA were functional. The data presented indicate that the MenPF-1 vaccine is a suitable formulation for presenting PorA and FetA OMPs in order to induce bactericidal antibodies, and that proceeding to a Phase I clinical trial with this vaccine candidate is justified.
authors.affiliation: National Institute of Biological Standards and Control, South Mimms, Potters Bar, United Kingdom.
authors.forename: Holly
authors.initials: H
authors.lastname: Sanders
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom; Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Gunnstein
authors.initials: G
authors.lastname: Norheim
authors.affiliation: National Institute of Biological Standards and Control, South Mimms, Potters Bar, United Kingdom.
authors.forename: Hannah
authors.initials: H
authors.lastname: Chan
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
authors.forename: Christina
authors.initials: C
authors.lastname: Dold
authors.affiliation: National Institute of Biological Standards and Control, South Mimms, Potters Bar, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Vipond
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester, United Kingdom.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Derrick
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
authors.affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Martin C J
authors.initials: MC
authors.lastname: Maiden
authors.affiliation: National Institute of Biological Standards and Control, South Mimms, Potters Bar, United Kingdom.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Feavers
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000276:immunology*; D004195:Disease Models, Animal; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007114:Immunization; D008585:Meningitis, Meningococcal / Q000276:immunology*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D009154:Mutation; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics* / Q000276:immunology*; D018272:Porins / Q000235:genetics; D011401:Promoter Regions, Genetic; D011817:Rabbits
chemical_list: D001425:Bacterial Outer Membrane Proteins; C093120:FrpB protein, bacteria; D022401:Meningococcal Vaccines; D018272:Porins; C057699:porin protein, Neisseria