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Discovery of Self‐Assembling Small Molecules as Vaccine Adjuvants

Kou Hioki, PhD candidate of CBMS, and Prof. Ken ISHII (Division of Vaccine Science, Department of Infection and Immunology) published a paper together with Prof. Uesugi, at Kyoto University about ‘Discovery of Self‐Assembling Small Molecules as Vaccine Adjuvants’ published in Angewandte Chemie International Edition (IF=19.959/2019)  
https://doi.org/10.1002/anie.202011604

Discovery of Self‐Assembling Small Molecules as Vaccine Adjuvants
Abstract
Immune potentiators, termed adjuvant, trigger early innate immune responses to ensure the generation of robust and long‐lasting adaptive immune responses of vaccines. Here we present 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 nano‐assembly potently elicits innate immune responses in macrophages and dendritic cells. Functional and mechanistic analyses indicate that the virus‐like assembly is engulfed inside 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 paves the way for a new approach to discovering and designing self‐assembling small‐molecule adjuvants against pathogens, including emerging viruses.

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