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

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DOIResolve DOI: http://doi.org/10.1016/j.vaccine.2012.05.006
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TypeArticle
Journal titleVaccine
ISSN0264410X
Volume30
Issue32
Pages48494858; # of pages: 10
SubjectCPSIII, group B streptococcal capsular polysaccharide type III; GBS, group B streptococci; GD3, glycan Neu5Ac(α2-8)Neu5Ac(α2-3)Gal (β1-4)Glc; GT3, glycan Neu5Ac(α2-8)Neu5Ac (α2-8)Neu5Ac(-α2-3)Gal(β1-4)Glc; PAA, polyacrylamide
AbstractGroup 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.
Publication date
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
IdentifierS0264410X12006792
NPARC number21268766
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Record identifier083ff8ce-4b78-4a7d-8da8-2d88412eaa68
Record created2013-11-12
Record modified2016-05-09
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