小分子
疫苗佐剂
纳米技术
自组装
化学
计算生物学
材料科学
佐剂
生物
免疫学
生物化学
作者
Jin Shuyu,Hue Thi Vu,Hioki Kou,Naotaka Noda,Hiroki Yoshida,Shimane Toru,Shigenari Ishizuka,Ippei Takashima,Toshio Kubota,Kathleen Beverly Pe,Tetsuya Ogawa,Naoya Nishimura,Daniel M. Packwood,Norihiro Tokitoh,Hiroki Kurata,Sho Yamasaki,Ken Ishii,Motonari Uesugi
标识
DOI:10.1002/anie.202011604
摘要
Immune potentiators, termed adjuvants, trigger early innate immune responses to ensure the generation of robust and long-lasting adaptive immune responses of vaccines. Presented here is a study that takes advantage of a self-assembling small-molecule library for the development of a novel vaccine adjuvant. Cell-based screening of the library and subsequent structural optimization led to the discovery of a simple, chemically tractable deoxycholate derivative (molecule 6, also named cholicamide) whose well-defined nanoassembly potently elicits innate immune responses in macrophages and dendritic cells. Functional and mechanistic analyses indicate that the virus-like assembly enters the cells and stimulates the innate immune response through Toll-like receptor 7 (TLR7), an endosomal TLR that detects single-stranded viral RNA. As an influenza vaccine adjuvant in mice, molecule 6 was as potent as Alum, a clinically used adjuvant. The studies described here pave the way for a new approach to discovering and designing self-assembling small-molecule adjuvants against pathogens, including emerging viruses.
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