title: Characterization of fHbp, nhba (gna2132), nadA, porA, sequence type (ST), and genomic presence of IS1301 in group B meningococcal ST269 clonal complex isolates from England and Wales.
abstract: Highly effective glycoconjugate vaccines exist against four of the five major pathogenic groups of meningococci: A, C, W-135, and Y. An equivalent vaccine against group B meningococci (menB) has remained elusive due to the poorly immunogenic capsular polysaccharide. A promising alternative, the investigational recombinant menB (rMenB)- outer membrane vesicle (OMV) vaccine, contains fHBP, NHBA (previously GNA2132), NadA, and outer membrane vesicles (OMVs) from the New Zealand MeNZB vaccine. MenB currently accounts for 90% of meningococcal disease in England and Wales, where the multilocus sequence type (ST) 269 (ST269) clonal complex (cc269) has recently expanded to account for a third of menB cases. To assess the potential cc269 coverage of the rMenB-OMV vaccine, English and Welsh cc269 isolates from the past decade were genetically characterized with respect to fHBP, NHBA, and NadA. All of the isolates harbored fHbp and nhba alleles, while 98% of the cc269 isolates were devoid of nadA. Subvariant profiling of fHbp, nhba, and porA against STs revealed the presence of two broadly distinct and well-defined clusters of isolates, centered around ST269 and ST275, respectively. An additional molecular marker, insertion sequence IS1301, was found to be present in 100% and <2% of isolates of the respective clusters. On the basis of the genetic data, the potential rMenB-OMV coverage of cc269 in England and Wales is high (up to 100%) within both clusters. Expression studies and serum bactericidal antibody assays will serve to enhance predictions of coverage and will augment ongoing studies regarding the significance of IS1301 within the ST269 cluster.
authors.affiliation: Vaccine Evaluation Unit, Health Protection Agency, P.O. Box 209, Floor 2, Clinical Sciences Building 2, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WZ, 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: Elisabeth
authors.initials: E
authors.lastname: Kugelberg
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: Christoph M
authors.initials: CM
authors.lastname: Tang
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D015373:Bacterial Typing Techniques; D016000:Cluster Analysis; D016172:DNA Fingerprinting; D004251:DNA Transposable Elements; D004739:England / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008589:Meningococcal Infections / Q000453:epidemiology* / Q000382:microbiology* / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000276:immunology; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000145:classification* / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014852:Wales / Q000453:epidemiology
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D022401:Meningococcal Vaccines