title: Antibody to genome-derived neisserial antigen 2132, a Neisseria meningitidis candidate vaccine, confers protection against bacteremia in the absence of complement-mediated bactericidal activity.
abstract: Genome-derived neisserial antigen 2132 (GNA2132) is a novel vaccine candidate that was identified during the Neisseria meningitidis group B strain MC58 genome-sequencing project. To assess the vaccine potential of GNA2132, we prepared antisera from mice immunized with recombinant GNA2132 (gene from strain NZ394/98). Anti-GNA2132 antibody bound to the surface of live bacteria from all 7 capsular group B or C strains tested and elicited deposition of human C3b on the bacterial surface. However, with human or infant-rat complement, anti-GNA2132 had no detectable bactericidal activity (titer, <1:4) against the nominal strain, NZ394/98, and was bactericidal against only 2 of the other 6 strains tested. These differences between strains were unrelated to GNA2132 amino acid sequence or level of protein expression. Despite lack of bactericidal activity, anti-GNA2132 antiserum passively protected infant rats against meningococcal bacteremia after challenge with all 5 resistant strains. GNA2132 is thus a promising vaccine candidate for prevention of disease caused by N. meningitidis.
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
authors.forename: Jo Anne
authors.initials: JA
authors.lastname: Welsch
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Moe
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rossi
authors.forename: Jeannette
authors.initials: J
authors.lastname: Adu-Bobie
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Dan M
authors.initials: DM
authors.lastname: Granoff
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial / Q000276:immunology*; D016470:Bacteremia / Q000517:prevention & control*; D001770:Blood Bactericidal Activity; D015153:Blotting, Western; D003165:Complement System Proteins / Q000502:physiology*; D005260:Female; D007106:Immune Sera / Q000276:immunology; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology*; D051381:Rats
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007106:Immune Sera; D022401:Meningococcal Vaccines; D003165:Complement System Proteins