title: Potential of recombinant opa proteins as vaccine candidates against hyperinvasive meningococci.
abstract: Neisseria meningitidis causes half a million cases of septicemia and meningitis globally each year. The opacity (Opa) integral outer membrane proteins from N. meningitidis are polymorphic and highly immunogenic. Particular combinations of Opa proteins are associated with the hyperinvasive meningococcal lineages that have caused the majority of serogroup B and C meningococcal disease in industrialized countries over the last 60 years. For the first time, this genetic structuring of a diverse outer membrane protein family has been used to select a novel combination of representative antigens for immunogenicity testing. Fourteen recombinant Opa variants were produced and used in murine immunizations inducing an increase in specific antimeningococcal total IgG levels. All 14 Opa proteins elicited bactericidal antibodies against at least one hyperinvasive meningococcal isolate, and most isolates from each hyperinvasive lineage were killed by at least one Opa antiserum at a titer of 1:16 or greater. Cross-reactive bactericidal antibody responses were observed among clonal complexes. A theoretical coverage of 90% can be achieved by using a particular combination of 6 Opa proteins against an isolate collection of 227 recent United Kingdom disease cases. This study indicates the potential of Opa proteins to provide broad coverage against multiple meningococcal hyperinvasive lineages.
authors.affiliation: Department of Paediatrics, University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom.
authors.forename: M J
authors.initials: MJ
authors.lastname: Callaghan
authors.forename: S
authors.initials: S
authors.lastname: Lewis
authors.forename: M
authors.initials: M
authors.lastname: Sadarangani
authors.forename: S E S
authors.initials: SE
authors.lastname: Bailey
authors.forename: H
authors.initials: H
authors.lastname: Chan
authors.forename: D J P
authors.initials: DJ
authors.lastname: Ferguson
authors.forename: J P
authors.initials: JP
authors.lastname: Derrick
authors.forename: I
authors.initials: I
authors.lastname: Feavers
authors.forename: M C
authors.initials: MC
authors.lastname: Maiden
authors.forename: A J
authors.initials: AJ
authors.lastname: Pollard
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D011994:Recombinant Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C090348:Opa protein, Neisseria