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Journal Article

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

MPS-Authors
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Broecker,  Felix
Chakkumal Anish, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Hanske,  Jonas
Christoph Rademacher, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Martin,  Christopher E.
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Baek,  Ju Yuel
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Wahlbrink,  Annette
Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Wojcik,  Felix
Laura Hartmann, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Hartmann,  Laura
Laura Hartmann, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Rademacher,  Christoph
Christoph Rademacher, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Chakkumkal,  Anish
Chakkumal Anish, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Seeberger,  Peter H.
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Fulltext (public)

2271521.pdf
(Publisher version), 2MB

Supplementary Material (public)

2271521_supp.pdf
(Supplementary material), 4MB

Citation

Broecker, F., Hanske, J., Martin, C. E., Baek, J. Y., Wahlbrink, A., Wojcik, F., et al. (2016). Multivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans. Nature Communications, 7: 11224. doi:10.1038/ncomms11224.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002A-41A9-E
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.