title: Sequence diversity of the factor H binding protein vaccine candidate in epidemiologically relevant strains of serogroup B Neisseria meningitidis.
abstract: BACKGROUND
  Recombinant forms of Neisseria meningitidis human factor H binding protein (fHBP) are undergoing clinical trials in candidate vaccines against invasive meningococcal serogroup B disease. We report an extensive survey and phylogenetic analysis of the diversity of fhbp genes and predicted protein sequences in invasive clinical isolates obtained in the period 2000-2006.
  
  
  METHODS
  Nucleotide sequences of fhbp genes were obtained from 1837 invasive N. meningitidis serogroup B (MnB) strains from the United States, Europe, New Zealand, and South Africa. Multilocus sequence typing (MLST) analysis was performed on a subset of the strains.
  
  
  RESULTS
  Every strain contained the fhbp gene. All sequences fell into 1 of 2 subfamilies (A or B), with 60%-75% amino acid identity between subfamilies and at least 83% identity within each subfamily. One fHBP sequence may have arisen via inter-subfamily recombination. Subfamily B sequences were found in 70% of the isolates, and subfamily A sequences were found in 30%. Multiple fHBP variants were detected in each of the common MLST clonal complexes. All major MLST complexes include strains in both subfamily A and subfamily B.
  
  
  CONCLUSIONS
  The diversity of strains observed underscores the importance of studying the distribution of the vaccine antigen itself rather than relying on common epidemiological surrogates such as MLST.
authors.affiliation: Wyeth Vaccines Research, Pearl River, New York 10965, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Murphy
authors.forename: Lubomira
authors.initials: L
authors.lastname: Andrew
authors.forename: Kwok-Leung
authors.initials: KL
authors.lastname: Lee
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Dilts
authors.forename: Lorna
authors.initials: L
authors.lastname: Nunez
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Fink
authors.forename: Karita
authors.initials: K
authors.lastname: Ambrose
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Jamie
authors.initials: J
authors.lastname: Findlow
authors.forename: Muhamed-Kheir
authors.initials: MK
authors.lastname: Taha
authors.forename: Ala-Eddine
authors.initials: AE
authors.lastname: Deghmane
authors.forename: Paula
authors.initials: P
authors.lastname: Kriz
authors.forename: Martin
authors.initials: M
authors.lastname: Musilek
authors.forename: Jitka
authors.initials: J
authors.lastname: Kalmusova
authors.forename: Dominique A
authors.initials: DA
authors.lastname: Caugant
authors.forename: Torill
authors.initials: T
authors.lastname: Alvestad
authors.forename: Leonard W
authors.initials: LW
authors.lastname: Mayer
authors.forename: Claudio T
authors.initials: CT
authors.lastname: Sacchi
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Diana
authors.initials: D
authors.lastname: Martin
authors.forename: Anne
authors.initials: A
authors.lastname: von Gottberg
authors.forename: Mignon
authors.initials: M
authors.lastname: du Plessis
authors.forename: Keith P
authors.initials: KP
authors.lastname: Klugman
authors.forename: Annaliesa S
authors.initials: AS
authors.lastname: Anderson
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.forename: Gary W
authors.initials: GW
authors.lastname: Zlotnick
authors.forename: Susan K
authors.initials: SK
authors.lastname: Hoiseth
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005060:Europe / Q000453:epidemiology; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D014644:Genetic Variation; D006801:Humans; D008585:Meningitis, Meningococcal / Q000453:epidemiology / Q000382:microbiology*; D022401:Meningococcal Vaccines / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D009520:New Zealand / Q000453:epidemiology; D013019:South Africa / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; C484699:factor H-binding protein, Neisseria meningitidis