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Discovery of Self‐Assembling Small Molecules as Vaccine Adjuvants
Author(s) -
Jin Shuyu,
Vu Hue Thi,
Hioki Kou,
Noda Naotaka,
Yoshida Hiroki,
Shimane Toru,
Ishizuka Shigenari,
Takashima Ippei,
Mizuhata Yoshiyuki,
Beverly Pe Kathleen,
Ogawa Tetsuya,
Nishimura Naoya,
Packwood Daniel,
Tokitoh Norihiro,
Kurata Hiroki,
Yamasaki Sho,
Ishii Ken J.,
Uesugi Motonari
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202011604
Subject(s) - adjuvant , vaccine adjuvant , immune system , tlr7 , innate immune system , acquired immune system , small molecule , biology , endosome , pattern recognition receptor , receptor , toll like receptor , immunology , biochemistry
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.