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合成糖以改进现有糖缀合物疫苗并对抗抗微生物药物耐药性。

Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance.

机构信息

GSK, R&D, Via Fiorentina 1, 53100 Siena, Italy.

Leiden Institute of Chemistry, Leiden University, 2300 RA Leiden, The Netherlands.

出版信息

Chem Rev. 2022 Oct 26;122(20):15672-15716. doi: 10.1021/acs.chemrev.2c00021. Epub 2022 May 24.

Abstract

Antimicrobial resistance (AMR) is emerging as the next potential pandemic. Different microorganisms, including the bacteria , , , , , , , non-typhoidal , and , and the fungus , have been identified by the WHO and CDC as urgent or serious AMR threats. Others, such as group A and B , are classified as concerning threats. Glycoconjugate vaccines have been demonstrated to be an efficacious and cost-effective measure to combat infections against , , , and, more recently, . Recent times have seen enormous progress in methodologies for the assembly of complex glycans and glycoconjugates, with developments in synthetic, chemoenzymatic, and glycoengineering methodologies. This review analyzes the advancement of glycoconjugate vaccines based on synthetic carbohydrates to improve existing vaccines and identify novel candidates to combat AMR. Through this literature survey we built an overview of structure-immunogenicity relationships from available data and identify gaps and areas for further research to better exploit the peculiar role of carbohydrates as vaccine targets and create the next generation of synthetic carbohydrate-based vaccines.

摘要

抗菌药物耐药性(AMR)正在成为下一个潜在的大流行病。世界卫生组织(WHO)和疾病控制与预防中心(CDC)已经确定了不同的微生物,包括细菌、、、、、、、非伤寒、和、和真菌,它们是紧急或严重的 AMR 威胁。其他微生物,如 A 组和 B 组,则被归类为令人关注的威胁。糖缀合物疫苗已被证明是对抗、、、和最近的的感染的有效且具有成本效益的措施。近年来,在复杂聚糖和糖缀合物的组装方法方面取得了巨大进展,在合成、化学酶和糖工程方法方面取得了进展。这篇综述分析了基于合成碳水化合物的糖缀合物疫苗的进展,以改进现有疫苗并确定新型候选物来对抗 AMR。通过这项文献调查,我们从现有数据中构建了一个关于结构-免疫原性关系的概述,并确定了差距和进一步研究的领域,以更好地利用碳水化合物作为疫苗靶点的特殊作用,并创造下一代基于合成碳水化合物的疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c2a/9614730/7085799b69bc/cr2c00021_0001.jpg

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