Epitopes recognized by a nonautoreactive murine anti-N-propionyl meningococcal group B polysaccharide monoclonal antibody.
The capsular polysaccharide of Neisseria meningitidis group B (MBPS) is a polymer of alpha (2-->8) N-acetyl neuraminic acid. The polysaccharide is chemically identical to an autoantigen, polysialic acid (PSA), and is a poor immunogen, even when conjugated to protein carriers. Immunization of mice with MBPS-protein conjugate vaccines, in which N-acetyl groups have been replaced by propionyl groups (N-Pr MBPS), elicits serum bactericidal antibodies. A subpopulation of these antibodies do not cross-react with human PSA. The reasons for the increased immunogenicity of N-Pr MBPS and the antigenic targets of the bactericidal nonautoreactive antibodies are unknown. In this study, we investigated the antigenic targets of a protective murine monoclonal antibody (MAb) prepared against a N-Pr MBPS-tetanus toxoid conjugate vaccine. Binding of the MAb to N-Pr MBPS (as demonstrated by an enzyme-linked immunosorbent assay) and bactericidal activity were inhibited by de-N-acetylated MBPS and re-N-acetylated MBPS, which indicate that N-propionyl groups are not obligatory determinants for binding. The results of affinity selection from a preparation of N-Pr MBPS and matrix-assisted laser desorption ionization-time of flight mass spectroscopic analysis indicated that the minimal epitope recognized by the MAb is a MBPS disaccharide containing one de-N-acetylated residue. Thus, the bacterial capsular epitope recognized by this bactericidal, nonautoreactive, anti-group-B MAb likely contains de-N-acetyl residues.
Moe
Gregory R
GR
Children's Hospital Oakland Research Institute, Oakland, California, USA. gmoe@chori.org
Dave
Apurva
A
Granoff
Dan M
DM
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D016667:Bacterial Capsules; D018604:Epitope Mapping; D009682:Magnetic Resonance Spectroscopy; D022401:Meningococcal Vaccines / Q000276:immunology; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018074:Vaccines, Conjugate / Q000276:immunology
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate; C039455:capsular polysaccharide, meningococcal group B