Natural and synthetic carbohydrate-based vaccine adjuvants and their mechanisms of action.
Natural and synthetic carbohydrate-based vaccine adjuvants and their mechanisms of action.
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作为自我辅助癌症疫苗的 Tn-RC-529 衍生物缀合物的全合成和生物活性评估
DOI：
10.1038/s41570-020-00244-3
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Fernández-Tejada A
中科院分区：
文献类型：
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作者：
Pifferi C;Fuentes R;Fernández-Tejada A
与传统的全病原体疫苗相比，基于同质抗原的现代亚单位疫苗提供更精确的靶向和更高的安全性。然而，它们的免疫原性也较低，并且需要佐剂来增加抗原的免疫原性并增强免疫应答。不幸的是，很少有佐剂具有足够的效力和足够低的毒性用于临床使用，这凸显了对新的、有效且安全的佐剂的迫切需求。值得注意的是，许多天然和合成的碳水化合物结构已在临床试验中用作佐剂，最近有两种已被批准用于人类疫苗。然而，天然衍生的碳水化合物佐剂是异质的，难以获得，并且在某些情况下不稳定。此外，它们的分子作用机制通常没有完全理解，部分原因是缺乏阐明其免疫增强作用的工具，从而阻碍了优化佐剂的合理开发。为了应对这些挑战，使用合成化学修饰天然产物结构成为开发定义明确的、改进的含碳水化合物佐剂和用于机理研究的化学探针的有吸引力的方法。本综述介绍了天然和合成碳水化合物为基础的佐剂及其在合成自我佐剂疫苗中的应用，同时还讨论了目前对其分子作用机制的理解。碳水化合物佐剂通过多种机制增强免疫应答。这篇综述强调了基于碳水化合物的佐剂，提供了对疫苗开发中的结构-活性关系和应用的见解，同时讨论了它们增强和调节免疫反应的机制的当前知识。
Modern subunit vaccines based on homogeneous antigens offer more precise targeting and improved safety compared with traditional whole-pathogen vaccines. However, they are also less immunogenic and require an adjuvant to increase the immunogenicity of the antigen and potentiate the immune response. Unfortunately, few adjuvants have sufficient potency and low enough toxicity for clinical use, highlighting the urgent need for new, potent and safe adjuvants. Notably, a number of natural and synthetic carbohydrate structures have been used as adjuvants in clinical trials, and two have recently been approved in human vaccines. However, naturally derived carbohydrate adjuvants are heterogeneous, difficult to obtain and, in some cases, unstable. In addition, their molecular mechanisms of action are generally not fully understood, partly owing to the lack of tools to elucidate their immune-potentiating effects, thus hampering the rational development of optimized adjuvants. To address these challenges, modification of the natural product structure using synthetic chemistry emerges as an attractive approach to develop well-defined, improved carbohydrate-containing adjuvants and chemical probes for mechanistic investigation. This Review describes selected examples of natural and synthetic carbohydrate-based adjuvants and their application in synthetic self-adjuvanting vaccines, while also discussing current understanding of their molecular mechanisms of action. Carbohydrate adjuvants potentiate immune responses through diverse mechanisms. This Review highlights carbohydrate-based adjuvants, providing insights into structure–activity relationships and applications in vaccine development, while discussing current knowledge of the mechanisms by which they potentiate and modulate the immune response.