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用于构建均质糖疫苗的精确蛋白质偶联技术。

Precise protein conjugation technology for the construction of homogenous glycovaccines.

机构信息

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal.

Departamento de Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química, E-26006 Logroño, Spain.

出版信息

Drug Discov Today Technol. 2020 Dec;38:69-75. doi: 10.1016/j.ddtec.2020.11.007. Epub 2021 Mar 18.

Abstract

The introduction of vaccines for the treatment and prevention of bacterial or viral diseases in the early 19th century marked a crucial turning point in medical history. Since then, extensive immunization campaigns have eradicated smallpox and drastically reduced the number of diphtheria, tetanus, pertussis and measles cases worldwide. Although a broad selection of vaccines is available, there remains a need to develop additional vaccine candidates against a range of dangerous infectious diseases, preferably based on precise syntheses that lead to homogenous formulations. Different strategies for the construction of this type of vaccine candidates are being pursued. Glycoconjugate vaccines are successful in the fight against bacterial and viral infectious diseases. However, their exact mechanism of action remains largely unknown and the large-scale production of chemically defined constructs is challenging. In particular, the conjugation of the carbohydrate antigen to the protein carrier has proved to be crucial for the properties of these vaccines. This review highlights some of the latest findings and developments in the construction of glycoconjugate vaccines by means of site-specific chemical reactions.

摘要

19 世纪初,疫苗的出现用于治疗和预防细菌或病毒疾病,这标志着医学史上的一个关键转折点。从那时起,广泛的免疫接种活动根除了天花,并大大减少了全球范围内白喉、破伤风、百日咳和麻疹的病例数。尽管有广泛的疫苗选择,但仍需要针对一系列危险传染病开发额外的疫苗候选物,最好是基于导致同质制剂的精确合成。正在寻求构建这类疫苗候选物的不同策略。糖缀合物疫苗在对抗细菌和病毒传染病方面取得了成功。然而,其确切的作用机制在很大程度上仍然未知,并且大规模生产化学定义的构建体具有挑战性。特别是,糖抗原与蛋白载体的缀合已被证明对这些疫苗的性质至关重要。本文通过特异性化学反应,重点介绍了糖缀合物疫苗构建方面的一些最新发现和进展。

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