Fine specificity and cross-reactions of monoclonal antibodies to group B streptococcal capsular polysaccharide type III.
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.
Research Institute for Children, Children's Hospital, New Orleans, LA 70118, United States. spincus@chnola-research.org
Seth H
SH
Pincus
Emily
E
Moran
Grace
G
Maresh
Harold J
HJ
Jennings
David G
DG
Pritchard
Marianne L
ML
Egan
Ola
O
Blixt
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D016667:Bacterial Capsules / Q000276:immunology; D002241:Carbohydrates / Q000276:immunology; D002460:Cell Line; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D007790:Lactosylceramides / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000276:immunology*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D002241:Carbohydrates; D005732:Gangliosides; D007790:Lactosylceramides; D011135:Polysaccharides, Bacterial; C032263:streptococcal polysaccharide type III group B; C026226:ganglioside, GD3; C047989:trisialosyllactosylceramide