Cross-protection in Neisseria meningitidis 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 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 indi...

Full description

Saved in:
Bibliographic Details
Published in:Carbohydrate research 2017-06, Vol.446-447, p.40-47
Main Authors: Kuttel, Michelle M., Timol, Zaheer, Ravenscroft, Neil
Format: Article
Language:English
Subjects:
Bacterial Vaccines - immunology
Capsular polysaccharide
Carbohydrate antigens
Carbohydrate Conformation
Carbohydrate Sequence
Cross Reactions
Cross-protection
Meningococcus
Molecular Dynamics Simulation
Molecular modelling
Neisseria meningitidis
Neisseria meningitidis - immunology
Polysaccharides, Bacterial - chemistry
Polysaccharides, Bacterial - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. [Display omitted] •Simulation of polysaccharide conformation in meningococcal serogroups Y and W.•Significant serogroup conformational differences in the α(2 → 6) linkage.•Y has one dominant conformation; W has a family of conformations.•Simulation data corroborated by NMR NOESY contacts.•Differences may explain different levels of cross-protection for Y and W vaccines.
ISSN:0008-6215
1873-426X
DOI:10.1016/j.carres.2017.05.004