title: Characterization of the key antigenic components and pre-clinical immune responses to a meningococcal disease vaccine based on Neisseria lactamica outer membrane vesicles.
abstract: Serogroup B strains are now responsible for over 80% of meningococcal disease in the UK and no suitable vaccine is available that confers universal protection against all serogroup B strains. Neisseria lactamica shares many antigens with the meningococcus, except capsule and the surface protein PorA. Many of these antigens are thought to be responsible for providing cross-protective immunity to meningococcal disease. We have developed an N. lactamica vaccine using methods developed for meningococcal outer membrane vesicle (OMV) vaccines. The major antigenic components were identified by excision of 11 major protein bands from an SDS-PAGE gel, followed by mass spectrometric identification. These bands contained at least 22 proteins identified from an unassembled N. lactamica genome, 15 of which having orthologues in published pathogenic Neisseria genomes. Western blotting revealed that most of these bands were immunogenic, and antibodies to these proteins generally cross-reacted with N. meningitidis proteins. Sera from mice and rabbits immunized with either N. lactamica or N. meningitidis OMVs produced comparable cross-reactive ELISA titres against OMVs prepared from a panel of diverse meningococcal strains. Mice immunized with either N. meningitidis or N. lactamica OMVs showed no detectable serum bactericidal activity against the panel of target strains except N. meningitidis OMV sera against the homologous strain. Similarly, rabbit antisera to N. lactamica OMVs elicited little or no bactericidal antibodies against the panel of serogroup B meningococcal strains. However, such antisera did mediate opsonophagocytosis, suggestingthat this may did mediate opsonophagocytosis, suggesting that this may be a mechanism by which this vaccine protects in a mouse model of meningococcal bacteraemia.
authors.affiliation: Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, UK. michelle.finney@hpa.org.uk
authors.forename: Michelle
authors.initials: M
authors.lastname: Finney
authors.forename: Thomas
authors.initials: T
authors.lastname: Vaughan
authors.forename: Stephen
authors.initials: S
authors.lastname: Taylor
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hudson
authors.forename: Catherine
authors.initials: C
authors.lastname: Pratt
authors.forename: Jun X
authors.initials: JX
authors.lastname: Wheeler
authors.forename: Caroline
authors.initials: C
authors.lastname: Vipond
authors.forename: Ian
authors.initials: I
authors.lastname: Feavers
authors.forename: Christopher
authors.initials: C
authors.lastname: Jones
authors.forename: Jamie
authors.initials: J
authors.lastname: Findlow
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Andrew
authors.initials: A
authors.lastname: Gorringe
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects* / Q000276:immunology; D008589:Meningococcal Infections / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D042806:Neisseria lactamica / Q000235:genetics* / Q000276:immunology; D011817:Rabbits
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D022401:Meningococcal Vaccines