title: Preclinical immunogenicity study of trivalent meningococcal AWX-OMV vaccines for the African meningitis belt.
abstract: In the recent decade, epidemic meningitis in the African meningitis belt has mostly been caused by Neisseria meningitidis of serogroups A, W and X (MenA, MenW and MenX, respectively). There is at present no licensed vaccine available to prevent MenX meningococcal disease. To explore a trivalent MenAWX vaccine concept, we have studied the immunogenicity in mice of MenX outer membrane vesicles (X-OMV) or MenX polysaccharide (X-PS) when combined with a bivalent A-OMV and W-OMV (AW-OMV) vaccine previously shown to be highly immunogenic in mice. The vaccine antigens were produced from three representative wild type strains of MenA (ST-7), MenW (ST-11) and MenX (ST-751) isolated from patients in the African meningitis belt. Groups of mice were immunized with two doses of X-OMV or X-PS combined with the AW-OMV vaccine or as individual components. All vaccine preparations were adsorbed to Al(OH)3. Sera from immunized mice were tested by ELISA and immunoblotting. Functional antibody responses were measured as serum bactericidal activity (SBA) and opsonophagocytic activity (OPA). Immunization of mice with X-OMV, alone or in combination with AW-OMV induced high levels of anti-X OMV IgG. Moreover, X-OMV alone or in combination with the AW-OMV vaccine induced high SBA and OPA titers against the MenX target strain. X-PS alone was not immunogenic in mice; however, addition of the AW-OMV vaccine to X-PS increased the immunogenicity of X-PS. Both AWX vaccine formulations induced high levels of IgG against A- and W-OMV and high SBA titers against the MenA and MenW vaccine strains. These results suggest that a trivalent AWX vaccine, either as a combination of OMV or OMV with X-PS, could potentially prevent the majority of meningococcal disease in the meningitis belt.
authors.affiliation: Norwegian Institute of Public Health, Division of Infectious Disease Control, P.O. Box 4404 Nydalen, 0403 Oslo, Norway. gro.tunheim@fhi.no
authors.forename: G
authors.initials: G
authors.lastname: Tunheim
authors.forename: L M
authors.initials: LM
authors.lastname: Naess
authors.forename: R
authors.initials: R
authors.lastname: Acevedo
authors.forename: Å K
authors.initials: ÅK
authors.lastname: Fjeldheim
authors.forename: K
authors.initials: K
authors.lastname: Bolstad
authors.forename: L
authors.initials: L
authors.lastname: García
authors.forename: D
authors.initials: D
authors.lastname: Cardoso
authors.forename: A
authors.initials: A
authors.lastname: Aase
authors.forename: C
authors.initials: C
authors.lastname: Zayas
authors.forename: H
authors.initials: H
authors.lastname: González
authors.forename: E
authors.initials: E
authors.lastname: Rosenqvist
authors.forename: G
authors.initials: G
authors.lastname: Norheim
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000349:Africa; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001770:Blood Bactericidal Activity; D055252:Cell-Derived Microparticles / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015151:Immunoblotting; D008585:Meningitis, Meningococcal / Q000453:epidemiology / Q000382:microbiology* / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000276:immunology* / Q000302:isolation & purification*; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology* / Q000302:isolation & purification; D009895:Opsonin Proteins / Q000097:blood; D010587:Phagocytosis; D011135:Polysaccharides, Bacterial / Q000276:immunology; D065288:Serogroup; D017778:Vaccines, Combined / Q000276:immunology / Q000302:isolation & purification
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000907:Antibodies, Bacterial; D022401:Meningococcal Vaccines; D009895:Opsonin Proteins; D011135:Polysaccharides, Bacterial; D017778:Vaccines, Combined; C041524:aluminum sulfate