title: Characterization of fHbp, nhba (gna2132), nadA, porA, and sequence type in group B meningococcal case isolates collected in England and Wales during January 2008 and potential coverage of an investigational group B meningococcal vaccine.
abstract: Invasive disease caused by meningococcal capsular groups A, C, W-135, and Y is now preventable by means of glycoconjugate vaccines that target their respective polysaccharide capsules. The capsule of group B meningococci (MenB) is poorly immunogenic and may induce autoimmunity. Vaccines based on the major immunodominant surface porin, PorA, are effective against clonal epidemics but, thus far, have a limited scope of coverage against the wider MenB population at large. In an alternative approach, the first-generation, investigational, recombinant MenB (rMenB) plus outer membrane vesicle (OMV) (rMenB-OMV) vaccine contains a number of relatively conserved surface proteins, fHBP, NHBA (previously GNA2132), and NadA, alongside PorA P1.4-containing OMVs from the New Zealand MeNZB vaccine. MenB currently accounts for approximately 90% of cases of meningococcal disease in England and Wales. To assess potential rMenB-OMV vaccine coverage of pathogenic MenB isolates within this region, all English and Welsh MenB case isolates from January 2008 (n = 87) were genetically characterized with respect to fHBP, NHBA, NadA, and PorA. Alleles for fHbp, nhba, and porA were identified in all of the isolates, of which 22% were also found to harbor nadA alleles. On the basis of genotypic data and predicted immunological cross-reactivity, the potential level of rMenB-OMV vaccine coverage in England and Wales ranges from 66% to 100%.
authors.affiliation: Vaccine Evaluation Unit, Health Protection Agency, P.O. Box 209, Floor 2, Clinical Sciences Building 2, Manchester Royal Infirmary, Oxford Road, Manchester M139WZ, United Kingdom. jay.lucidarme@hpa.org.uk
authors.forename: Jay
authors.initials: J
authors.lastname: Lucidarme
authors.forename: Maurizio
authors.initials: M
authors.lastname: Comanducci
authors.forename: Jamie
authors.initials: J
authors.lastname: Findlow
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gray
authors.forename: Edward B
authors.initials: EB
authors.lastname: Kaczmarski
authors.forename: Malcolm
authors.initials: M
authors.lastname: Guiver
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Vallely
authors.forename: Philipp
authors.initials: P
authors.lastname: Oster
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.forename: Stefania
authors.initials: S
authors.lastname: Bambini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Muzzi
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000483:Alleles; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004739:England / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008589:Meningococcal Infections / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D038541:Neisseria meningitidis, Serogroup B / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D018272:Porins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014852:Wales / Q000453:epidemiology
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; C501982:NadA protein, Neisseria meningitidis; D018272:Porins; D014614:Vaccines, Synthetic; C484699:factor H-binding protein, Neisseria meningitidis; C057699:porin protein, Neisseria