title: Effect of sequence variation in meningococcal PorA outer membrane protein on the effectiveness of a hexavalent PorA outer membrane vesicle vaccine.
abstract: Though meningococcal serogroup C conjugate vaccines have been introduced into the UK infant immunisation schedule, there is currently no vaccine solution for serogroup B disease. PorA outer membrane protein (OMP) is a potential serogroup B vaccine candidate. A hexavalent PorA outer membrane vesicle (OMV) vaccine has been evaluated in phase I and II trials with promising results. This vaccine contains six different PorA OMPs each representing a different serosubtype. However, considerable sequence variation occurs in the variable regions (VRs) encoding these serosubtypes. By using recombinant P1.5,10 PorA variants we have demonstrated that the killing of this particular serosubtype combination was due mainly to the induction of antibody to the VR2 (P1.10) epitope region, and that after three or four doses of vaccine there was a significant reduction in the killing of variants P1.10a (three doses, p<0.0001; four doses, p = 0.003) and P1.10f (three doses, p<0.0001; four doses, p = 0.002), as compared to responses to the P1.10 strain, when the P1.10 serosubtype was used as the immunogen. Since large numbers of serosubtype variants are known to exist, this finding may have implications for the use of PorA as a meningococcal serogroup B vaccine.
authors.affiliation: Meningococcal Reference Unit, Manchester Public Health Laboratory, Withington Hospital, Nell Lane, Manchester M20 2LR, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Martin
authors.forename: R
authors.initials: R
authors.lastname: Borrow
authors.forename: P
authors.initials: P
authors.lastname: van der Ley
authors.forename: M
authors.initials: M
authors.lastname: Dawson
authors.forename: A J
authors.initials: AJ
authors.lastname: Fox
authors.forename: K A
authors.initials: KA
authors.lastname: Cartwright
mesh_terms: D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000940:Antigenic Variation; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002675:Child, Preschool; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D007223:Infant; D022401:Meningococcal Vaccines; D009345:Neisseria meningitidis / Q000145:classification / Q000235:genetics / Q000276:immunology*; D018272:Porins / Q000235:genetics / Q000276:immunology*; D012703:Serotyping; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D016056:Immunodominant Epitopes; D022401:Meningococcal Vaccines; D018272:Porins; D014614:Vaccines, Synthetic; C057699:porin protein, Neisseria