title: Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870.
abstract: Sepsis and meningitis caused by serogroup B meningococcus are devastating diseases of infants and young adults, which cannot yet be prevented by vaccination. By genome mining, we discovered GNA1870, a new surface-exposed lipoprotein of Neisseria meningitidis that induces high levels of bactericidal antibodies. The antigen is expressed by all strains of N. meningitidis tested. Sequencing of the gene in 71 strains representative of the genetic and geographic diversity of the N. meningitidis population, showed that the protein can be divided into three variants. Conservation within each variant ranges between 91.6 to 100%, while between the variants the conservation can be as low as 62.8%. The level of expression varies between strains, which can be classified as high, intermediate, and low expressors. Antibodies against a recombinant form of the protein elicit complement-mediated killing of the strains that carry the same variant and induce passive protection in the infant rat model. Bactericidal titers are highest against those strains expressing high yields of the protein; however, even the very low expressors are efficiently killed. The novel antigen is a top candidate for the development of a new vaccine against meningococcus.
authors.affiliation: IRIS, Chiron Srl, via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Vega
authors.initials: V
authors.lastname: Masignani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Comanducci
authors.forename: Marzia Monica
authors.initials: MM
authors.lastname: Giuliani
authors.forename: Stefania
authors.initials: S
authors.lastname: Bambini
authors.forename: Jeannette
authors.initials: J
authors.lastname: Adu-Bobie
authors.forename: Beatrice
authors.initials: B
authors.lastname: Arico
authors.forename: Brunella
authors.initials: B
authors.lastname: Brunelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pieri
authors.forename: Laura
authors.initials: L
authors.lastname: Santini
authors.forename: Silvana
authors.initials: S
authors.lastname: Savino
authors.forename: Davide
authors.initials: D
authors.lastname: Serruto
authors.forename: David
authors.initials: D
authors.lastname: Litt
authors.forename: Simon
authors.initials: S
authors.lastname: Kroll
authors.forename: Jo Anne
authors.initials: JA
authors.lastname: Welsch
authors.forename: Dan M
authors.initials: DM
authors.lastname: Granoff
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D005260:Female; D005798:Genes, Bacterial; D006801:Humans; D007223:Infant; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology* / Q000378:metabolism; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016415:Sequence Alignment; D014611:Vaccination
chemical_list: D000942:Antigens, Bacterial; D008074:Lipoproteins; D020033:Protein Isoforms; D011994:Recombinant Proteins