Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate
Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate
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DOI：
10.1016/j.vaccine.2010.09.018
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发表时间：
2010-12-10
期刊：
影响因子：
5.5
通讯作者：
Costantino, Paolo
中科院分区：
文献类型：
--
作者：
Kabanova, Anna;Margarit, Immaculada;Costantino, Paolo
由A组链球菌(GAS)引起的细菌感染是一个严重的卫生保健问题，目前无法通过接种疫苗预防。GAS细胞壁多糖(GAS-PS)因其在不同细菌株上的恒定表达模式和抗GAS-PS抗体的保护性而成为一种有吸引力的疫苗候选。在这里，我们首次报道了与含有天然GAS-PS的糖偶联物相比，合成GAS寡糖的免疫保护效果。采用化学合成法合成了一系列基于GAS-PS结构的六糖和十二糖，并将其与CRM197偶联。当在小鼠身上测试时，含有合成低聚糖的结合物提供了与天然结合物相当的免疫保护水平。免疫兔抗血清可促进包膜GAS菌株的吞噬功能。此外，我们讨论了可能与糖共轭免疫原性相关的变量，并展示了合成方法的潜力，这种合成方法受益于提高抗原纯度和简化制造。(C)2010爱思唯尔有限公司。保留所有权利。
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. (C) 2010 Elsevier Ltd. All rights reserved.