title: Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing.
abstract: Neisseria meningitidis is a major cause of bacterial septicemia and meningitis. Sequence variation of surface-exposed proteins and cross-reactivity of the serogroup B capsular polysaccharide with human tissues have hampered efforts to develop a successful vaccine. To overcome these obstacles, the entire genome sequence of a virulent serogroup B strain (MC58) was used to identify vaccine candidates. A total of 350 candidate antigens were expressed in Escherichia coli, purified, and used to immunize mice. The sera allowed the identification of proteins that are surface exposed, that are conserved in sequence across a range of strains, and that induce a bactericidal antibody response, a property known to correlate with vaccine efficacy in humans.
authors.affiliation: IRIS, Chiron S.p.A., Via Fiorentina 1, 53100 Siena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pizza
authors.forename: V
authors.initials: V
authors.lastname: Scarlato
authors.forename: V
authors.initials: V
authors.lastname: Masignani
authors.forename: M M
authors.initials: MM
authors.lastname: Giuliani
authors.forename: B
authors.initials: B
authors.lastname: Aricò
authors.forename: M
authors.initials: M
authors.lastname: Comanducci
authors.forename: G T
authors.initials: GT
authors.lastname: Jennings
authors.forename: L
authors.initials: L
authors.lastname: Baldi
authors.forename: E
authors.initials: E
authors.lastname: Bartolini
authors.forename: B
authors.initials: B
authors.lastname: Capecchi
authors.forename: C L
authors.initials: CL
authors.lastname: Galeotti
authors.forename: E
authors.initials: E
authors.lastname: Luzzi
authors.forename: R
authors.initials: R
authors.lastname: Manetti
authors.forename: E
authors.initials: E
authors.lastname: Marchetti
authors.forename: M
authors.initials: M
authors.lastname: Mora
authors.forename: S
authors.initials: S
authors.lastname: Nuti
authors.forename: G
authors.initials: G
authors.lastname: Ratti
authors.forename: L
authors.initials: L
authors.lastname: Santini
authors.forename: S
authors.initials: S
authors.lastname: Savino
authors.forename: M
authors.initials: M
authors.lastname: Scarselli
authors.forename: E
authors.initials: E
authors.lastname: Storni
authors.forename: P
authors.initials: P
authors.lastname: Zuo
authors.forename: M
authors.initials: M
authors.lastname: Broeker
authors.forename: E
authors.initials: E
authors.lastname: Hundt
authors.forename: B
authors.initials: B
authors.lastname: Knapp
authors.forename: E
authors.initials: E
authors.lastname: Blair
authors.forename: T
authors.initials: T
authors.lastname: Mason
authors.forename: H
authors.initials: H
authors.lastname: Tettelin
authors.forename: D W
authors.initials: DW
authors.lastname: Hood
authors.forename: A C
authors.initials: AC
authors.lastname: Jeffries
authors.forename: N J
authors.initials: NJ
authors.lastname: Saunders
authors.forename: D M
authors.initials: DM
authors.lastname: Granoff
authors.forename: J C
authors.initials: JC
authors.lastname: Venter
authors.forename: E R
authors.initials: ER
authors.lastname: Moxon
authors.forename: G
authors.initials: G
authors.lastname: Grandi
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016667:Bacterial Capsules; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology; D017124:Conserved Sequence; D004926:Escherichia coli / Q000235:genetics; D016680:Genome, Bacterial; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D051379:Mice; D009345:Neisseria meningitidis / Q000145:classification / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D016366:Open Reading Frames; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D012703:Serotyping; D014611:Vaccination; D014774:Virulence
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D007106:Immune Sera; D011993:Recombinant Fusion Proteins