Multivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans

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Abstract

Synthetic cell-surface glycans are promising vaccine candidates against Clostridium difficile. The complexity of large, highly antigenic and immunogenic glycans is a synthetic challenge. Less complex antigens providing similar immune responses are desirable for vaccine development. Based on molecular-level glycan-antibody interaction analyses, we here demonstrate that the C. 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. We show that 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 small oligosaccharides to achieve antigenicity characteristic of larger glycans. The approach may result in more cost-efficient carbohydrate vaccines with reduced synthetic effort.

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APA

Broecker, F., Hanske, J., Martin, C. E., Baek, J. Y., Wahlbrink, A., Wojcik, F., … Seeberger, P. H. (2016). Multivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans. Nature Communications, 7. https://doi.org/10.1038/ncomms11224

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