Kuttel MM, Timol Z, Ravenscroft N Cross-protection in Neisseria meningitidis serogroups Y and W polysaccharides: A comparative conformational analysis Carbohydrate Research (2017)
40-47
/Variants 0/-+
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-6)-a-D-Galp-(1-4)-a-Neup5Ac-(2-
/Variants 0/ is:
?%Ac-9)-
OR (exclusively)
?%Ac-7)-
NCBI PubMed ID:28501716 Publication DOI:10.1016/j.carres.2017.05.004 Journal NLM ID:0043535 Publisher: Elsevier Correspondence: mkuttelcs.uct.ac.za Institutions: Department of Computer Science, University of Cape Town, Cape Town, 7701, South Africa
The capsular polysaccharide is the main virulence factor in meningococcus. The capsular polysaccharides for meningococcal serogroups Y and W are almost identical polymers of hexose-sialic acid, suggesting the possibility of cross-protection between group Y and W vaccines. However, early studies indicated that they elicit different levels of cross-protection. Here we explore the conformations of the meningococcal Y and W polysaccharides with molecular dynamics simulations of three repeating unit oligosaccharide strands. We find differences in Y and W antigen conformation: the Y polysaccharide has a single dominant conformation, whereas W exhibits a family of conformations including the Y conformation. This result is supported by our NMR NOESY analysis, which indicates key close contacts for W that are not present in Y. These conformational differences provide an explanation for the different levels of cross-protection measured for the Y and W monovalent vaccines and the high group W responses observed in HibMenCY-TT vaccinees.
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