Multivalent Display of Minimal Clostridium difficile Glycan Epitopes Mimics Antigenic Properties of Larger Glycans

The complex glycans covering the surface of bacterial, viral and parasitic pathogens represent interesting target for vaccine developments. Glycoconjugate vaccines consisting of isolated polysaccharides have come a long way and prove, to be highly effective. Their development suffers from many hurdles among which the variability and the heterogeneity of the polysaccharides. An alternative route would be to use synthetic small glycans of controlled and reproducible structures a key feature in the designed and refinement of structure-based epitopes.

However, still remains the question whether such small glycans, eventually arranged to displaying multivalent features, may induce responses characteristic of larger glycans. The results reported in the article entitled : “Multivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans” provide a convincing answer to this question. The Clostridium difficile surface polysaccharide-I (PS-I) can be resembled by multivalent display of minimal disaccharide epitopes on a synthetic scaffold that does not participate in binding. The antibody avidity, as a measure of antigenicity, increases by about five orders of magnitude when disaccharides are compared with constructs containing five disaccharides. The synthetic, pentavalent vaccine candidate containing a peptide T-cell epitope elicits weak but highly specific antibody responses to larger PS-I glycans in mice. This study highlights the potential of multivalently displaying smalloligosaccharides to achieve antigenicity characteristic of larger glycans. The approach may result in more cost-efficient carbohydrate vaccines with reduced synthetic effort.