Group B streptococcus (GBS) is a major cause of neonatal sepsis and meningitis. Despite aggressive campaigns using antenatal prophylactic antibiotic therapy, infections continue. Developing an effective maternal vaccine is a public health priority. Antibody (Ab) to the capsular polysaccharide (CPS) is considered the dominant 'protective' immune mediator. Here we study the fine specificity and potential host reactivity of a panel of well-characterized murine monoclonal Abs against the type III CPS by examining the binding of the Abs to intact and neuraminidase-digested GBS, purified CPS, synthetic carbohydrate structures, and cells. The results showed marked differences in the fine specificity among these mAbs to a single carbohydrate structure. Cross-reactions with synthetic GD3 and GT3 carbohydrates, representing structures found on surfaces of neural and developing cells, were demonstrated using carbohydrate array technology. The anti-CPS(III) mAbs did not react with cells expressing GD3 and GT3, nor did mAbs specific for the host carbohydrates cross-react with GBS, raising questions about the physiological relevance of this cross-reaction. But in the process of these investigations, we serendipitously demonstrated cross-reactions of some anti-CPS(III) mAbs with antigens, likely carbohydrates, found on human leukocytes. These studies suggest caution in the development of a maternal vaccine to prevent infection by this important human pathogen.
capsular polysaccharide, group B Streptococcus, cross-reaction, monoclonal Ab, fine specificity, carbohydrate array
NCBI PubMed ID: 22634296Publication DOI: 10.1016/j.vaccine.2012.05.006Journal NLM ID: 8406899Publisher: Elsevier
Correspondence: spincus@chnola-research.org
Institutions: Research Institute for Children, Children's Hospital, New Orleans, LA 70118, United States, Institute for Biological Sciences, National Research Council of Canada, Ottawa, ON, Canada K1A 0R6, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, United States, Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, United States, Copenhagen Center for Glycomics (CCG), Departments of Cellular and Molecular Medicine and Dentistry, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark
Methods: ELISA, biological assays, serological methods, binding assays, immunofluorescence analyses
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