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 as tudy that takes advantage of as elfassembling small-molecule library for the development of an ovel vaccine adjuvant. Cell-based screening of the library and subsequent structural optimization led to the discovery of as imple,c hemically tractable deoxycholate derivative (molecule 6,a lso named cholicamide) whose well-defined nanoassembly potently elicits innate immune responses in macrophages and dendritic cells.F unctional 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 singlestranded viral RNA. As an influenza vaccine adjuvant in mice, molecule 6 was as potent as Alum, ac linically used adjuvant. The studies described here pave the way for anew approachto discovering and designing self-assembling small-molecule adjuvants against pathogens,i ncluding emerging viruses.

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Phase-separated membraneless organelles or biomolecular condensates play diverse functions in cells, however recapturing their characteristics using small organic molecules has been a challenge. In the present study, cell-lysate-based screening of...