Multivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans
Felix Broecker,
Jonas Hanske,
Christopher E. Martin,
Ju Yuel Baek,
Annette Wahlbrink,
Felix Wojcik,
Laura Hartmann,
Christoph Rademacher,
Chakkumkal Anish () and
Peter H. Seeberger ()
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Felix Broecker: Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park
Jonas Hanske: Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park
Christopher E. Martin: Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park
Ju Yuel Baek: Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park
Annette Wahlbrink: Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park
Felix Wojcik: Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park
Laura Hartmann: Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park
Christoph Rademacher: Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park
Chakkumkal Anish: Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park
Peter H. Seeberger: Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park
Nature Communications, 2016, vol. 7, issue 1, 1-12
Abstract:
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.
Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11224
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DOI: 10.1038/ncomms11224
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