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Infection and Immunity, April 2002, p. 1724-1738, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.1724-1738.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Type III Group B Streptococcal Polysaccharide Induces Antibodies That Cross-React with Streptococcus pneumoniae Type 14

Hilde-Kari Guttormsen,^1* Carol J. Baker,² Moon H. Nahm,^3, Lawrence C. Paoletti,¹ Susu M. Zughaier,^1, Morven S. Edwards,² and Dennis L. Kasper^1,4

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital,¹ Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115,⁴ Section of Infectious Diseases, Department of Pediatrics and of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030,² Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642³

Received 8 October 2001/ Returned for modification 10 December 2001/ Accepted 21 December 2001

Covalent linkage of a bacterial polysaccharide to a protein greatly enhances the carbohydrate's immunogenicity and its binding to solid surfaces in immunoassays. These findings have spurred the development of glycoconjugate vaccines to prevent serious bacterial infections as well as the use of glycoconjugates as coating antigens in bioassays. We evaluated sera from women immunized with unconjugated group B streptococcal (GBS) type III (GBS III) polysaccharide (IIIPS) or with IIIPS covalently linked to tetanus toxoid to assess specificity, sensitivity, and parallelism in dilution curves in two GBS III enzyme-linked immunosorbent assays (ELISAs). One assay used IIIPS mixed with methylated human serum albumin (IIIPS + mHSA) as the coating antigen, and the other used IIIPS covalently linked to HSA (III-HSA). Each coating antigen was associated with a highly specific GBS III bioassay. The sensitivity was higher in the III-HSA ELISA, in which conjugated IIIPS is bound to the plates. Parallelism in titration curves was observed in the III-HSA but not in the IIIPS + mHSA ELISA. The excellent correlation between the concentrations of GBS IIIPS-specific immunoglobulin G (IgG) and the opsonophagocytic activity of these antibodies indicated that the III-HSA assay can predict functionality of vaccine-induced IgG against GBS III disease. The structure of the repeating unit of the capsular polysaccharide of GBS III differs from that of Streptococcus pneumoniae type 14 (Pn14 PS) only by the presence on GBS III of a sialic acid residue at the end of the side chain. The majority of healthy adults responding to GBS III vaccines with a fourfold or greater increase in GBS III-specific IgG antibodies developed antibodies cross-reacting with Pn14 PS (i.e., desialylated GBS IIIPS). The proportion of GBS vaccine responders who developed IgG to the desialylated IIIPS did not depend on whether IIIPS was given in the unconjugated or conjugated form. When present, these vaccine-induced cross-reacting antibodies conferred in vitro antibody-mediated opsonophagocytosis and killing of both GBS III and Pn14, two pathogens that cause invasive disease in young infants.

Editor: E. I. Tuomanen

Present address: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294.

Present address: Department of Microbiology and Immunology, Emory University Medical School, Atlanta, GA 30303.

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