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タイトル: | Discovery of Self‐Assembling Small Molecules as Vaccine Adjuvants |
著者: | Jin, Shuyu Vu, Hue Thi Hioki, Kou Noda, Naotaka Yoshida, Hiroki Shimane, Toru Ishizuka, Shigenari Takashima, Ippei Mizuhata, Yoshiyuki https://orcid.org/0000-0001-5301-0024 (unconfirmed) Pe, Kathleen Beverly Ogawa, Tetsuya Nishimura, Naoya Packwood, Daniel Tokitoh, Norihiro https://orcid.org/0000-0003-1083-7245 (unconfirmed) Kurata, Hiroki https://orcid.org/0000-0002-0682-1227 (unconfirmed) Yamasaki, Sho Ishii, Ken J Uesugi, Motonari https://orcid.org/0000-0002-8515-445X (unconfirmed) |
著者名の別形: | 日置, 仰 野田, 尚孝 吉田, 大樹 島根, 徹 石塚, 茂宜 高嶋, 一平 水畑, 吉行 小川, 哲也 西村, 直矢 パックウッド, ダニエル 時任, 宣博 倉田, 博基 山崎, 晶 石井, 健 上杉, 志成 |
キーワード: | Chemical biology self-assembly Toll-like receptor |
発行日: | 11-Jan-2021 |
出版者: | Wiley |
誌名: | Angewandte Chemie International Edition |
巻: | 60 |
号: | 2 |
開始ページ: | 961 |
終了ページ: | 969 |
抄録: | 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. |
記述: | 自己集合性ワクチンアジュバントの発見. 京都大学プレスリリース. 2020-10-07. Vaccine ingredients could be hiding in small molecule libraries. 京都大学プレスリリース. 2020-10-07. |
著作権等: | This is the peer reviewed version of the following article: S. Jin, H. T. Vu, K. Hioki, N. Noda, H. Yoshida, T. Shimane, S. Ishizuka, I. Takashima, Y. Mizuhata, K. Beverly Pe, T. Ogawa, N. Nishimura, D. Packwood, N. Tokitoh, H. Kurata, S. Yamasaki, K. J. Ishii, M. Uesugi, Angew. Chem. Int. Ed. 2021, 60, 961, which has been published in final form at https://doi.org/10.1002/anie.202011604. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. The full-text file will be made open to the public on 3 November 2021 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/261692 |
DOI(出版社版): | 10.1002/anie.202011604 |
PubMed ID: | 32979004 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research/research_results/2020/200926_2.html https://www.kyoto-u.ac.jp/en/research/research_results/2020/200926_2.html |
出現コレクション: | 学術雑誌掲載論文等 |
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