Cross-protection in Neisseria meningitidis serogroups Y and W polysaccharides: A comparative conformational analysis

Carbohydrate Research
Michelle M KuttelNeil Ravenscroft

Abstract

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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Citations

Jun 11, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Michelle M KuttelStefan Oscarson
Mar 25, 2020·The Journal of Physical Chemistry. B·Jason HlozekMichelle Mary Kuttel
Sep 19, 2019·Journal of Chemical Information and Modeling·Roy González-AlemánLuis A Montero-Cabrera
Apr 26, 2018·Journal of Chemical Theory and Computation·Asaminew H AytenfisuAlexander D MacKerell

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