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

Academic Article

Abstract

  • 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. © 2012 Elsevier Ltd.
  • Authors

    Published In

  • Vaccine  Journal
  • Digital Object Identifier (doi)

    Author List

  • Pincus SH; Moran E; Maresh G; Jennings HJ; Pritchard DG; Egan ML; Blixt O
  • Start Page

  • 4849
  • End Page

  • 4858
  • Volume

  • 30
  • Issue

  • 32