title: Variability of genes encoding surface proteins used as vaccine antigens in meningococcal endemic and epidemic strain panels from Norway.
abstract: Surface-expressed protein antigens such as factor H-binding protein (fHbp), Neisserial adhesin A (NadA), Neisserial heparin-binding antigen (NHBA) and Porin protein A (PorA); all express sequence variability that can affect their function as protective immunogens when used in meningococcal serogroup B vaccines like the recently-approved 4CMenB (Bexsero(®)). We assessed the sequence variation of genes coding for these proteins and two additional proteins ("fusion partners" to fHbp and NHBA) in pathogenic isolates from a recent low incidence period (endemic situation; 2005-2006) in Norway. Findings among strains from this panel were contrasted to what was found among isolates from a historic outbreak (epidemic situation; 1985-1990). Multilocus sequence typing revealed 14 clonal complexes (cc) among the 66 endemic strains, while cc32 vastly predominated in the 38-strain epidemic panel. Serogroup B isolates accounted for 50/66 among endemic strains and 28/38 among epidemic strains. Potential strain-coverage ("sequence match") for the 4CMenB vaccine was identified among the majority (>70%) of the endemic serogroup B isolates and all of the epidemic serogroup B isolates evaluated. Further information about the degree of expression, surface availability and the true cross-reactivity for the vaccine antigens will be needed to fully characterize the clinical strain-coverage of 4CMenB in various geographic and epidemiological situations.
authors.affiliation: Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway. Electronic address: johan.holst@fhi.no.
authors.forename: Johan
authors.initials: J
authors.lastname: Holst
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Comanducci
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bambini
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Muzzi
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy. Electronic address: comandi80@gmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Comandi
authors.affiliation: Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Oksnes
authors.affiliation: Novartis Vaccines and Diagnostics, Cambridge, USA. Electronic address: lisadetora@hotmail.com.
authors.forename: Lisa
authors.initials: L
authors.lastname: DeTora
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.affiliation: Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway; Section for International Health, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Dominique A
authors.initials: DA
authors.lastname: Caugant
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics* / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D015373:Bacterial Typing Techniques; D058872:Epidemics; D060005:Genotyping Techniques; D006801:Humans; D008585:Meningitis, Meningococcal / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000235:genetics*; D058885:Multilocus Sequence Typing; D038541:Neisseria meningitidis, Serogroup B / Q000145:classification* / Q000235:genetics; D009664:Norway; D010802:Phylogeny; D018272:Porins / Q000235:genetics / Q000276:immunology
chemical_list: C570015:4CMenB vaccine; D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; C501982:NadA protein, Neisseria meningitidis; D018272:Porins; C484699:factor H-binding protein, Neisseria meningitidis; C057699:porin protein, Neisseria
keywords: MenB vaccine; Meningococcal disease; Neisseria meningitidis; Vaccine evaluation