Multivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans.
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.
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park, 14476 Potsdam, Germany.|Department of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Felix
F
Broecker
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park, 14476 Potsdam, Germany.|Department of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Jonas
J
Hanske
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park, 14476 Potsdam, Germany.|Department of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Christopher E
CE
Martin
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park, 14476 Potsdam, Germany.
Ju Yuel
JY
Baek
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park, 14476 Potsdam, Germany.
Annette
A
Wahlbrink
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park, 14476 Potsdam, Germany.
Felix
F
Wojcik
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park, 14476 Potsdam, Germany.
Laura
L
Hartmann
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park, 14476 Potsdam, Germany.|Department of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Christoph
C
Rademacher
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park, 14476 Potsdam, Germany.
Chakkumkal
C
Anish
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam-Golm Science Park, 14476 Potsdam, Germany.|Department of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Peter H
PH
Seeberger
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D015153:Blotting, Western; D016360:Clostridioides difficile / Q000276:immunology* / Q000502:physiology; D004187:Disaccharides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D004761:Enterocolitis, Pseudomembranous / Q000097:blood / Q000276:immunology / Q000382:microbiology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006001:Glycoconjugates / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D007114:Immunization / Q000379:methods; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D004187:Disaccharides; D018984:Epitopes, T-Lymphocyte; D006001:Glycoconjugates; D011134:Polysaccharides; D014614:Vaccines, Synthetic