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Infection and Immunity, December 2005, p. 7887-7893, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.7887-7893.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

National Institute of Child Health and Human Development,¹ National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892,³ Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow, Idaho 83844,² Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892⁴

Received 28 June 2005/ Returned for modification 22 July 2005/ Accepted 26 August 2005

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.

Editor: J. N. Weiser