Immunochemical analysis and immunogenicity of the type II group B streptococcal capsular polysaccharide.

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Abstract

The relationship between group B streptococcal (GBS) type-specific antisera and the type II-specific polysaccharide is evaluated from a structural and immunologic viewpoint. Although all GBS type-specific polysaccharides are composed of the same monosaccharides, the type II antigen is more complex structurally and contains these sugars in a molar ratio different from the other antigens. Type II polysaccharide has two side chains. One contains only sialic acid and is less susceptible to acid cleavage than sialic acid residues found on types III, Ia, and Ib polysaccharides. The other side chain is composed of galactose as the only sugar. Immunochemical studies demonstrate that the type II polysaccharide has several immunodeterminants. One of these determinants is likely to be the side-chain galactose, while sialic acid appears to comprise part of another immunodeterminant, more complex than sialic acid alone. A series of cross-reactions is demonstrated between the type II native antigen and antisera to serotypes Ia, III, and Ib by a sensitive radioactive antigen-binding assay, which account for additional, complex immunodeterminants. The strongest of these cross-reactions is with type Ia antiserum and the weakest with Ib antiserum. Since Ia and Ib polysaccharides differ in only one linkage, these findings suggest that the trisaccharide beta D-N-acetyl-glucosamine-p(1 leads to 3) beta D-galactose-p(1 leads to 4) beta D-glucose-p [[beta D-GlcNAcp(1 leads to 3) beta D-Galp(1 leads to 4)beta D-Glcap]] is the likely common site responsible for the interaction of the type II native polysaccharide and type Ia antiserum. Another cross-reaction is observed between type III antiserum and type II native antigen. Inhibition studies indicate that the most likely cross-reactive determinant in this case is [beta D-Galp(1 leads to 4)beta D-GlcNAcp]. Type II polysaccharide has been utilized in a human vaccine trial to test safety and immunogenicity. The polysaccharide is highly immunogenic, inducing an antibody response in 95% of recipients, and nontoxic, with side-effects confined to minimal local reactions. Despite the cross-reactions observed between type-specific antigens and antibody prepared by immunization of rabbits with whole bacteria, which suggest shared immunodeterminants, similar cross-reactions were not detected in human sera after immunization with purified type II polysaccharide.

Authors

D L Kasper, C J Baker, B Galdes, E Katzenellenbogen, H J Jennings