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链长至关重要:基于QS-21的高效疫苗佐剂的研发

Chain Length Does Matter: Development of High-Potency QS-21-Based Vaccine Adjuvants.

作者信息

Luo Zhikuan, Wang Hong, Ge Wanwan, Wang Yuping, Zhou Shijun, Jing Ruijun, Siddique Muhammad Nasir, Ma Xusheng, Zheng Haixue, Wang Xiaolei

机构信息

State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou University, Lanzhou 730000, PR China.

State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730000, PR China.

出版信息

J Med Chem. 2025 Jan 23;68(2):1511-1525. doi: 10.1021/acs.jmedchem.4c02173. Epub 2025 Jan 2.

Abstract

Adjuvants are crucial agents that enhance the immunogenicity of vaccines, with QS-21 being particularly noteworthy for its potent immunostimulatory properties. QS-21, a saponin-based vaccine adjuvant isolated from the bark of , has garnered significant attention. However, its application as vaccine adjuvant is limited due to its scarcity, complex chemical synthesis, and inherent toxicity. This study aims to develop QS-21 analogues with simplified structures, enhanced immunogenicity, and reduced toxicity. Our research findings indicate that the antibody titers generated by the analogues VA05 and VA06 in conjunction with the antigen are comparable to those induced by QS-21. With their lower toxicity, VA05 and VA06 emerge as promising candidates for next-generation adjuvant development, potentially surpassing QS-21 in both efficacy and safety.

摘要

佐剂是增强疫苗免疫原性的关键物质,其中QS-21因其强大的免疫刺激特性而格外引人注目。QS-21是一种从[植物名称]树皮中分离出的基于皂苷的疫苗佐剂,已引起广泛关注。然而,由于其稀缺性、复杂的化学合成过程以及内在毒性,其作为疫苗佐剂的应用受到限制。本研究旨在开发结构简化、免疫原性增强且毒性降低的QS-21类似物。我们的研究结果表明,类似物VA05和VA06与抗原联合产生的抗体滴度与QS-21诱导的相当。VA05和VA06毒性较低,有望成为下一代佐剂开发的候选物,在疗效和安全性方面可能超越QS-21。

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