Phosphorylation of the Synthetic Hexasaccharide Repeating Unit Is Essential for the Induction of Antibodies to Clostridium difficile PSII Cell Wall Polysaccharide

Clostridium difficile is emerging worldwide as a major cause of nosocomial infections. The negatively charged PSII polysaccharide has been found in different strains of C. difficile and, thereby, represents an important target molecule for a possible carbohydrate-based vaccine. In order to identify...

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Bibliographic Details
Published in:ACS chemical biology 2012-08, Vol.7 (8), p.1420-1428
Main Authors: Adamo, Roberto, Romano, Maria R, Berti, Francesco, Leuzzi, Rosanna, Tontini, Marta, Danieli, Elisa, Cappelletti, Emilia, Cakici, Osman S, Swennen, Erwin, Pinto, Vittoria, Brogioni, Barbara, Proietti, Daniela, Galeotti, Cesira L, Lay, Luigi, Monteiro, Mario A, Scarselli, Maria, Costantino, Paolo
Format: Article
Language:English
Subjects:
Animals
Anti-Infective Agents - pharmacology
Antibodies - chemistry
Carbohydrate Sequence
Carbohydrates - chemistry
Cell Wall - immunology
Clostridium difficile - immunology
Clostridium difficile - metabolism
Cross Infection - drug therapy
Humans
Magnetic Resonance Spectroscopy - methods
Mice
Microscopy, Confocal - methods
Models, Chemical
Molecular Sequence Data
Oligosaccharides - chemistry
Phosphorylation
Polysaccharides - chemistry
Vaccines - chemistry
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Summary:Clostridium difficile is emerging worldwide as a major cause of nosocomial infections. The negatively charged PSII polysaccharide has been found in different strains of C. difficile and, thereby, represents an important target molecule for a possible carbohydrate-based vaccine. In order to identify a synthetic fragment that after conjugation to a protein carrier could be able to induce anti-PSII antibodies, we exploited a combination of chemical synthesis with immunochemistry, confocal immunofluorescence microscopy, and solid state NMR. We demonstrate that the phosphate group is crucial in synthetic glycans to mimic the native PSII polysaccharide; both native PSII and a phosphorylated synthetic hexasaccharide repeating unit conjugated to CRM197 elicit comparable immunogenic responses in mice. This finding can aid design and selection of carbohydrate antigens to be explored as vaccine candidates.
ISSN:1554-8929
1554-8937
DOI:10.1021/cb300221f