title: Bactericidal monoclonal antibodies that define unique meningococcal B polysaccharide epitopes that do not cross-react with human polysialic acid.
abstract: The poor immunogenicity of the Neisseria meningitidis group B polysaccharide capsule, a homopolymer of alpha(2-->8) sialic acid, has been attributed to immunologic tolerance induced by prenatal exposure to host polysialyated glycoproteins. Substitution of N-propionyl (N-Pr) for N-acetyl groups on the meningococcal B polysaccharide, and conjugation of the resulting polysaccharide to a protein carrier, have been reported to yield a conjugate vaccine that elicits protective Abs with minimal autoantibody activity. To characterize the protective epitopes on the derivatized polysaccharide, we isolated 30 anti-N-Pr meningococcal B polysaccharide mAbs. These Abs were heterogeneous with respect to complement-mediated bactericidal activity, fine antigenic specificity, and autoantibody activity as defined by binding to the neuroblastoma cell line, CHP-134, which expresses long-chain a(2-->8)-linked polysialic acid. Eighteen of the Abs could activate complement-mediated bacteriolysis. Seven of these 18 Abs cross-reacted with N-acetyl meningococcal B polysaccharide by ELISA and had strong autoantibody activity. Thus, N-Pr meningococcal B polysaccharide conjugate vaccine has the potential to elicit autoantibodies. However, 7 of the 18 bactericidal mAbs had no detectable autoantibody activity. These Abs may be useful for the identification of molecular mimetics capable of eliciting protective Abs specific to the bacteria, without the risk of evoking autoimmune disease.
authors.affiliation: Chiron Vaccines, Emeryville, CA 94608, USA. dan_granoff@cc.chiron.com
authors.forename: D M
authors.initials: DM
authors.lastname: Granoff
authors.forename: A
authors.initials: A
authors.lastname: Bartoloni
authors.forename: S
authors.initials: S
authors.lastname: Ricci
authors.forename: E
authors.initials: E
authors.lastname: Gallo
authors.forename: D
authors.initials: D
authors.lastname: Rosa
authors.forename: N
authors.initials: N
authors.lastname: Ravenscroft
authors.forename: V
authors.initials: V
authors.lastname: Guarnieri
authors.forename: R C
authors.initials: RC
authors.lastname: Seid
authors.forename: A
authors.initials: A
authors.lastname: Shan
authors.forename: W R
authors.initials: WR
authors.lastname: Usinger
authors.forename: S
authors.initials: S
authors.lastname: Tan
authors.forename: Y E
authors.initials: YE
authors.lastname: McHugh
authors.forename: G R
authors.initials: GR
authors.lastname: Moe
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D003429:Cross Reactions; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D005260:Female; D006801:Humans; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D012794:Sialic Acids / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D000939:Epitopes; D011135:Polysaccharides, Bacterial; D012794:Sialic Acids; C021319:polysialic acid; D003165:Complement System Proteins