Comparative Molecular Modelling of Capsular Polysaccharide Conformations in Streptococcus suis Serotypes 1, 2, 1/2 and 14 Identifies Common Epitopes for Antibody Binding

Streptococcus suis is an encapsulated, commensal, potentially pathogenic bacterium that infects swine globally and causes sporadic life-threatening zoonotic septicemia and meningitis infections in humans. The capsular polysaccharide is a primary virulence factor for S. suis. As S. suis serotype 2 is the most prevalent serotype globally, the serotype 2 CPS is the primary target of current efforts to develop an effective glycoconjugate veterinary vaccine against S. suis. Possible cross-protection with related serotypes would broaden the coverage of a vaccine. The CPS in serotypes 2 and 1/2 differ at a single residue (Gal versus GalNAc), and both are similar to serotypes 1 and 14: all contain a terminal sialic acid on a side chain. However, despite this similarity, there is complex pattern of cross-protection for these serotypes, with varying estimations of the importance of sialic acid in a protective epitope. Further, a pentasaccharide without the terminal sialic acid has been identified as minimal epitope for serotype 2. Here we use molecular simulation to model the molecule conformations of the CPS in serotypes 2, 1/2, 1 and 14, as well as three vaccine candidate oligosaccharides. The common epitopes we identify assist in rationalizing the apparently contradictory immunological data and provide a basis for rational design of S. suis vaccines in the future.