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Fine specificity and cross-reactions of monoclonal antibodies to group B streptococcal capsular polysaccharide type III

Pincus, Seth H., Moran, Emily, Maresh, Grace, Jennings, Harold J., Pritchard, David G., Egan, Marianne L., Blixt, Ola
Vaccine 2012 v.30 no.32 pp. 4849-4858
Streptococcus agalactiae, antibiotics, antigens, carbohydrate structure, carbohydrates, cross reaction, humans, leukocytes, meningitis, mice, monoclonal antibodies, pathogens, public health, therapeutics, vaccines
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-CPSIII 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-CPSIII 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.