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

  作者 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  
  选自 期刊  ACS CHEMICAL BIOLOGY;  卷期  2012年7-8;  页码  1420-1428  
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[摘要]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

 
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