2021年1月11日
Discovery of Self‐Assembling Small Molecules as Vaccine Adjuvants
Angewandte Chemie International Edition
- 巻
- 60
- 号
- 2
- 開始ページ
- 961
- 終了ページ
- 969
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1002/anie.202011604
- 出版者・発行元
- Wiley
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.
- リンク情報
- ID情報
-
- DOI : 10.1002/anie.202011604
- ISSN : 1433-7851
- eISSN : 1521-3773
- PubMed ID : 32979004