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

详细信息    查看全文

• 作者：Roberto Adamo ; Maria R. Romano ; Francesco Berti ; Rosanna Leuzzi ; Marta Tontini ; Elisa Danieli ; Emilia Cappelletti ; Osman S. Cakici ; Erwin Swennen ; Vittoria Pinto ; Barbara Brogioni ; Daniela Proietti ; Cesira L. Galeotti ; Luigi Lay ; Mario A. Monteiro ; Maria Scarselli ; Paolo Costantino
• 刊名：ACS Chemical Biology
• 出版年：2012
• 出版时间：August 17, 2012
• 年：2012
• 卷：7
• 期：8
• 页码：1420-1428
• 全文大小：527K
• 年卷期：v.7,no.8(August 17, 2012)
• ISSN：1554-8937

文摘

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 CRMb>197b> elicit comparable immunogenic responses in mice. This finding can aid design and selection of carbohydrate antigens to be explored as vaccine candidates.