Cross protection in Neisseria meningitides serogroups Y and W polysaccharides: a comparative conformational analysis.

The capsular polysaccharide is the main virulence factor in meningococcus. The capsular polysaccharides for meningococcal serogroups Y andWare 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 forWthat are notpresent 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