Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 2, Pages 961-969Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202011604
Keywords
chemical biology; nanostructures; RNA; self-assembly; viruses
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Funding
- JSPS [17H06408, 19H00922]
- Kyoto University
- Grants-in-Aid for Scientific Research [17H06408, 19H00922] Funding Source: KAKEN
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A novel vaccine adjuvant utilizing a self-assembling small-molecule library was developed in this study, which strongly induced innate immune responses in macrophages and dendritic cells through activation of Toll-like receptor 7. Functional analyses showed that the adjuvant was as potent as the clinically used adjuvant Alum in mice as an influenza vaccine.
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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