title: Distribution of surface protein variants among hyperinvasive meningococci: implications for vaccine design.
abstract: The bacterium Neisseria meningitidis is a major cause of meningitis and septicemia worldwide. Outer membrane proteins (OMPs) are candidates in the search for comprehensive meningococcal vaccines; however, the formulation of OMP vaccines is complicated by antigenic diversity, which is generated by high levels of genetic reassortment and strong positive selection in the meningococcal antigen genes. The genetic and antigenic diversity of three OMPs (FetA, PorA, and PorB) among a global collection of meningococcal isolates representative of the major hyperinvasive clonal complexes was determined. There was evidence for antigenic structuring among the three OMPs that could not be explained purely by descent. These observations violated the predictions of the clonal and epidemic clonal models of population structure but were in concordance with models of strain structure which propose that host immunity selects for nonoverlapping antigen combinations. The patterns of antigenic variant combinations suggested that an OMP-based vaccine with as few as six PorA and five FetA variant sequences could generate homologous immune responses against all 78 isolates examined.
authors.affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom. rachel.urwin@zoo.ox.ac.uk
authors.forename: Rachel
authors.initials: R
authors.lastname: Urwin
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Russell
authors.forename: Emily A L
authors.initials: EA
authors.lastname: Thompson
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.forename: Ian M
authors.initials: IM
authors.lastname: Feavers
authors.forename: Martin C J
authors.initials: MC
authors.lastname: Maiden
mesh_terms: D000483:Alleles; D000940:Antigenic Variation / Q000235:genetics*; D000942:Antigens, Bacterial / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D019143:Evolution, Molecular; D005798:Genes, Bacterial / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005843:Geography; D006801:Humans; D008589:Meningococcal Infections / Q000382:microbiology / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000235:genetics / Q000276:immunology; D009345:Neisseria meningitidis / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D010802:Phylogeny; D018272:Porins / Q000235:genetics; D013997:Time Factors
chemical_list: D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D000939:Epitopes; C093120:FrpB protein, bacteria; D022401:Meningococcal Vaccines; D018272:Porins; C057699:porin protein, Neisseria