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含有合成肺炎链球菌荚膜多糖片段的糖微阵列及其在疫苗开发中的应用。

Glycan Microarrays Containing Synthetic Streptococcus pneumoniae CPS Fragments and Their Application to Vaccine Development.

机构信息

Department of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, Germany.

Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Berlin, Germany.

出版信息

Methods Mol Biol. 2022;2460:193-206. doi: 10.1007/978-1-0716-2148-6_12.

DOI:10.1007/978-1-0716-2148-6_12
PMID:34972938
Abstract

Streptococcus pneumoniae is the leading source of life-endangering diseases like pneumonia, septicemia, and meningitis, as well as a major cause of death in children under 5 years old in developing countries. At least 98 serotypes of S. pneumoniae can be distinguished based on their structurally distinct capsular polysaccharides (CPS). Currently available CPS-based pneumococcal vaccines contain serotypes most frequently associated with invasive pneumococcal diseases. The polysaccharides used in commercial conjugate-vaccines are isolated from bacteria cultures comprising many laborious and operationally challenging steps followed by depolymerization of long polysaccharides into small fragments and their conjugation to the carrier protein. The medicinal chemistry approach for glycoconjugate vaccine development offers an exciting alternative to CPS isolation for a broad range of different glycan antigens. Glycan arrays containing well-defined synthetic glycans of CPS fragments and repeating units are used as a platform for the high-throughput screening of various serum samples and identification of protective glycotopes for vaccine candidates.

摘要

肺炎链球菌是导致肺炎、败血症和脑膜炎等危及生命疾病的主要病原体,也是发展中国家 5 岁以下儿童死亡的主要原因。根据其结构上不同的荚膜多糖 (CPS),可以区分至少 98 种血清型的肺炎链球菌。目前可用的基于 CPS 的肺炎球菌疫苗包含与侵袭性肺炎球菌病最相关的血清型。商业结合疫苗中使用的多糖是从细菌培养物中分离出来的,包括许多繁琐且操作复杂的步骤,然后将长多糖降解成小片段,并将其与载体蛋白结合。糖缀合物疫苗开发的药物化学方法为广泛的不同聚糖抗原提供了 CPS 分离的另一种令人兴奋的选择。含有 CPS 片段和重复单元的明确合成聚糖的聚糖阵列被用作高通量筛选各种血清样本和鉴定候选疫苗的保护性糖基表位的平台。

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本文引用的文献

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Automated Glycan Assembly: A Perspective.自动化糖基化组装:一个视角。
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Microbe-focused glycan array screening platform.聚糖微阵列筛选平台。
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Improving vaccines against using synthetic glycans.利用合成糖脂改进疫苗。
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J Clin Microbiol. 2018 Feb 22;56(3). doi: 10.1128/JCM.01318-17. Print 2018 Mar.
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Semisynthetic glycoconjugate vaccine candidate against serotype 5.针对 5 型的半合成糖缀合物疫苗候选物。
Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):11063-11068. doi: 10.1073/pnas.1706875114. Epub 2017 Oct 2.