Serological and conformational properties of E. coli K92 capsular polysaccharide and its N-propionylated derivative both illustrate that induced antibody does not recognize extended epitopes of polysialic acid: Implications for a comprehensive conjugate vaccine towards Groups B and C N. meningitidis

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TypeArticle
Journal titleCanadian Journal of Chemistry
Volume80
Issue8
Pages10551063; # of pages: 9
SubjectACID; Antibodies; antibody; capsular polysaccharide; capsular polysaccharides; COMPONENT; conformation; CONFORMATIONAL; CONFORMATIONS; CONJUGATE VACCINE; DYNAMICS; epitope; Epitopes; Form; GROUP-B; MOLECULAR; MOLECULAR DYNAMICS; MOLECULAR-DYNAMICS; oligosaccharide; Oligosaccharides; POLYSACCHARIDE; Polysaccharides; protein
AbstractThe capsular polysaccharide of E. coli K92 (K92P) contains elements in common with the capsular polysaccharides of both groups B and C N. meningitidis , and may therefore form the basis of a bivalent vaccine. In an attempt to augment the cross-protective immune response to group B meningococci, the N -acetyl groups of the K92P were replaced by N -propionyl groups (NPrK92P) and conjugated to protein. This strategy had previously been applied with success to the poorly immunogenic capsular polysaccharide of group B meningococcus (GBMP), and the bactericidal epitope was found to be exclusively mimicked by extended helical segments of the NPrGBMP. The NPrK92P-conjugate, in relation to a K92P-conjugate, failed to enhance the response to GBMP but did generate a measurable response to NPrGBMP, but only at the expense of a greatly reduced GCMP response. Despite the presence of an immune response to NPrGBMP, the anti-NPrK92 serum was not bactericidal. Competitive inhibition studies with NPrGBMP oligosaccharides suggested the NPrK92 antibodies could not cross-react with the protective epitope on group B meningococci, as defined by extended helical segments of the NPrGBMP, but only recognized short non-bactericidal NPrGBMP epitopes. This hypothesis was supported from the conformational and molecular dynamics studies of the K92P, which demonstrated a lack of extended conformations that resemble the GBMP extended epitope. Indeed, the conformational properties of the K92P more closely resembled those of the GCMP, thereby explaining the observed moderate cross-protection of the K92P antiserum towards group C meningococci. Thus, on the basis of these results, it can be concluded that K92P, regardless of N -propionyl modification, will not serve as an effective single vaccine component against both groups B and C meningococci.
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NRC numberPON2002
NPARC number9372581
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Record identifier936f73e8-a253-476c-b5aa-9bf1728ada7a
Record created2009-07-10
Record modified2016-05-09
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