title: Conjugates of group A and W135 capsular polysaccharides of neisseria meningitidis bound to recombinant Staphylococcus aureus enterotoxin C1: preparation, physicochemical characterization, and immunological properties in mice.
abstract: Neisseria meningitidis groups A (GAM) and W135 capsular polysaccharides (CPs) were bound to recombinant Staphylococcus aureus enterotoxin C1 (rSEC). The CPs were activated with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate and then bound to adipic acid dihydrazide derivatives of rSEC. Syntheses were conducted with native GAM CP (GAMP), W135 CP (W135P), and ultrasonicated or hydrazine-treated W135P at various concentrations of reactants, pHs, and ionic strengths. The conjugates were characterized by compositional and serologic analyses, high-performance size-exclusion chromatography with multi-angle laser light scattering detection, and immunogenicity in 5- to 6-week-old mice. Conjugates injected subcutaneously in phosphate-buffered saline elicited immunoglobulin G (IgG) responses against their respective CPs and rSEC, whereas GAMP and W135P alone did not induce detectable CP antibodies. The O-acetyl content of W135P was low, and its removal had no adverse effect upon the conjugate's immunogenicity. Reduction of the molecular size of W135P by treatment with hydrazine improved the immunogenicity of W135P-rSEC. IgG anti-CP elicited by the conjugates showed complement-dependent bactericidal activity against their respective organisms, and IgG anti-rSEC neutralized the T-cell proliferative activity of native SEC. A bivalent formulation of GAMP-rSEC and W135P-rSEC elicited IgG anti-CP at comparable levels to those induced by the conjugates administered separately.
authors.affiliation: National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. jinz@mail.nih.gov
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Jin
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Bohach
authors.forename: Joseph
authors.initials: J
authors.lastname: Shiloach
authors.forename: Scott E
authors.initials: SE
authors.lastname: Norris
authors.forename: Darón I
authors.initials: DI
authors.lastname: Freedberg
authors.forename: Claudia
authors.initials: C
authors.lastname: Deobald
authors.forename: Bruce
authors.initials: B
authors.lastname: Coxon
authors.forename: John B
authors.initials: JB
authors.lastname: Robbins
authors.forename: Rachel
authors.initials: R
authors.lastname: Schneerson
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology; D004768:Enterotoxins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D022401:Meningococcal Vaccines / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D038381:Neisseria meningitidis, Serogroup A / Q000276:immunology*; D038582:Neisseria meningitidis, Serogroup W-135 / Q000276:immunology*; D009500:Neutralization Tests; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D004768:Enterotoxins; D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial; D011994:Recombinant Proteins; D018074:Vaccines, Conjugate; C034959:enterotoxin C, staphylococcal