Kuttel Michelle M, Timol Zaheer, Ravenscroft Neil
Department of Computer Science, University of Cape Town, Cape Town, 7701, South Africa.
Department of Chemistry, University of Cape Town, Cape Town, 7701, South Africa.
Carbohydr Res. 2017 Jun 29;446-447:40-47. doi: 10.1016/j.carres.2017.05.004. Epub 2017 May 10.
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.
荚膜多糖是脑膜炎球菌的主要毒力因子。Y群和W群脑膜炎球菌的荚膜多糖是几乎相同的己糖 - 唾液酸聚合物，这表明Y群和W群疫苗之间存在交叉保护的可能性。然而，早期研究表明它们引发的交叉保护水平不同。在这里，我们通过对三条重复单元寡糖链进行分子动力学模拟，探索脑膜炎球菌Y群和W群多糖的构象。我们发现Y群和W群抗原构象存在差异：Y群多糖具有单一的优势构象，而W群则呈现出包括Y群构象在内的一系列构象。我们的核磁共振NOESY分析支持了这一结果，该分析表明W群存在Y群中不存在的关键紧密接触。这些构象差异解释了Y群和W群单价疫苗交叉保护水平不同以及在HibMenCY-TT疫苗接种者中观察到的高W群反应。
