title: Preclinical immunogenicity and functional activity studies of an A+W meningococcal outer membrane vesicle (OMV) vaccine and comparisons with existing meningococcal conjugate- and polysaccharide vaccines.
abstract: Meningococci of serogroups A and W (MenA and MenW) are the main causes of epidemic bacterial meningitis outbreaks in sub-Saharan Africa. In this study we prepared a detergent extracted outer membrane vesicle (dOMV) vaccine from representative African MenA and MenW strains, and compared the immunogenicity of this vaccine with existing meningococcal conjugate and polysaccharide (PS) vaccines in mice. NMRI mice were immunized with preclinical batches of the A+W dOMV vaccine, or with commercially available vaccines; a MenA conjugate vaccine (MenAfriVac(®), Serum Institute of India), ACYW conjugate vaccine (Menveo(®), Novartis) or ACYW PS vaccine (Mencevax(®), GlaxoSmithKline). The mice received 2 doses of 1/10 or 1/50 of a human dose with a three week interval. Immune responses were tested in ELISA, serum bactericidal activity (SBA) and opsonophagocytic activity (OPA) assays. High levels of IgG antibodies against both A and W dOMV were detected in mice receiving the A+W dOMV vaccine. High SBA titers against both MenA and MenW vaccine strains were detected after only one dose of the A+W dOMV vaccine, and the titers were further increased after the second dose. The SBA and OPA titers in mice immunized with dOMV vaccine were significantly higher than in mice immunized with the ACYW-conjugate vaccine or the PS vaccine. Furthermore, the A+W dOMV vaccine was shown to induce SBA and OPA titers against MenA of the same magnitude as the titers induced by the A-conjugate vaccine. In conclusion, the A+W dOMV vaccine induced high levels of functional antibodies to both MenA and MenW strains, levels that were shown to be higher or equal to the levels induced by licensed meningococcal vaccines. Thus, an A+W dOMV vaccine could potentially serve as an alternative or a supplement to existing conjugate and PS vaccines in the African meningitis belt.
authors.affiliation: Norwegian Institute of Public Health (NIPH), P.O. Box 4404, Nydalen, 0403 Oslo, Norway. Electronic address: gro.tunheim@fhi.no.
authors.forename: G
authors.initials: G
authors.lastname: Tunheim
authors.forename: M
authors.initials: M
authors.lastname: Arnemo
authors.forename: L M
authors.initials: LM
authors.lastname: Næss
authors.forename: Å K
authors.initials: ÅK
authors.lastname: Fjeldheim
authors.forename: L
authors.initials: L
authors.lastname: Nome
authors.forename: K
authors.initials: K
authors.lastname: Bolstad
authors.forename: A
authors.initials: A
authors.lastname: Aase
authors.forename: A
authors.initials: A
authors.lastname: Mandiarote
authors.forename: H
authors.initials: H
authors.lastname: González
authors.forename: D
authors.initials: D
authors.lastname: González
authors.forename: L
authors.initials: L
authors.lastname: García
authors.forename: D
authors.initials: D
authors.lastname: Cardoso
authors.forename: G
authors.initials: G
authors.lastname: Norheim
authors.forename: E
authors.initials: E
authors.lastname: Rosenqvist
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D004353:Drug Evaluation, Preclinical; D005260:Female; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood; D008589:Meningococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D038381:Neisseria meningitidis, Serogroup A / Q000276:immunology*; D038582:Neisseria meningitidis, Serogroup W-135 / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Africa; Meningitis belt; Meningococcal disease; Neisseria meningitidis; OMV; OPA; Opsonophagocytic activity; Outer membrane protein; Outer membrane vesicle; SBA; Serum bactericidal activity; Vaccine