Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate

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• 作者：Anna Kabanova ; Immaculada Margarit ; Francesco Berti ; Maria R. Romano ; Guido Gr ; i ; Giuliano Bensi ; Emiliano Chiarot ; Daniela Proietti ; Erwin Swennen ; Emilia Cappelletti ; Paola Fontani ; Daniele Casini
• 关键词：Group A Streptococcus ; Glycoconjugate vaccine
• 刊名：Vaccine
• 出版年：2010
• 出版时间：10 December 2010
• 年：2010
• 卷：29
• 期：1
• 页码：104-114
• 全文大小：1179 K

文摘

Bacterial infections caused by Group A Streptococcus (GAS) are a serious health care concern that currently cannot be prevented by vaccination. The GAS cell-wall polysaccharide (GAS-PS) is an attractive vaccine candidate due to its constant expression pattern on different bacterial strains and protective properties of anti-GAS-PS antibodies. Here we report for the first time the immunoprotective efficacy of glycoconjugates with synthetic GAS oligosaccharides as compared to those containing the native GAS-PS. A series of hexa- and dodecasaccharides based on the GAS-PS structure were prepared by chemical synthesis and conjugated to CRM₁₉₇. When tested in mice, the conjugates containing the synthetic oligosaccharides conferred levels of immunoprotection comparable to those elicited by the native conjugate. Antisera from immunized rabbits promoted phagocytosis of encapsulated GAS strains. Furthermore we discuss variables that might correlate with glycoconjugate immunogenicity and demonstrate the potential of the synthetic approach that benefits from increased antigen purity and facilitated manufacturing.