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

Nat Commun. 2016 Apr 19:7:11224. doi: 10.1038/ncomms11224.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Antibody Formation / immunology
  • Antigens, Bacterial / immunology
  • Blotting, Western
  • Clostridioides difficile / immunology*
  • Clostridioides difficile / physiology
  • Disaccharides / chemistry
  • Disaccharides / immunology*
  • Disaccharides / metabolism
  • Enterocolitis, Pseudomembranous / blood
  • Enterocolitis, Pseudomembranous / immunology
  • Enterocolitis, Pseudomembranous / microbiology
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology*
  • Epitopes, T-Lymphocyte / metabolism
  • Female
  • Glycoconjugates / chemistry
  • Glycoconjugates / immunology
  • Glycoconjugates / metabolism
  • Host-Pathogen Interactions / immunology
  • Immunization / methods
  • Mice, Inbred C57BL
  • Molecular Structure
  • Polysaccharides / chemistry
  • Polysaccharides / immunology*
  • Polysaccharides / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology


  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Disaccharides
  • Epitopes, T-Lymphocyte
  • Glycoconjugates
  • Polysaccharides
  • Vaccines, Synthetic