Development of Highly Functionalized Lipid A and its Application to Innate and Acquired Immune Regulatory Molecules
| Project/Area Number |
20K05749
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 37030:Chemical biology-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | リピドA / リポ多糖 / アジュバント / セルフアジュバンティングワクチン / 抗原-アジュバント複合体 / LNP / 糖鎖ミミックリンカー / 細菌-宿主間ケミカルエコロジー / 抗原－アジュバント複合体 / 細菌‐宿主間ケミカルエコロジー / ケミカルエコロジー / 高次機能化 / 自然-獲得免疫制御分子 |
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| Outline of Research at the Start |
近年、抗原とアジュバントの複合化により、効率的な抗体産生が誘導されることが報告され、有望なアジュバント候補であるリピドAと抗原を複合化した合成ワクチンの開発に注目が集まっているが、活性を保持可能なリピドAの修飾法は十分には検討されていない。本研究では、天然LPS構造を模倣する戦略により活性を保持可能なリピドA修飾法を検討し、自然免疫活性化に加え第二の機能を付加した高次機能化リピドAの合成戦略を確立する、さらには自然・獲得免疫を同時に制御可能な分子を創製する。
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| Outline of Final Research Achievements |
We hypothesized that symbiotic bacteria would contain useful immunomodulators with low toxicity, and conducted chemical synthesis and functional analysis of intestinal Peyer's patches symbiotic bacterial lipid A. We found that this symbiotic bacterial lipid A is very promising as a mucosal vaccine adjuvant.
On the other hand, a self-adjuvant effect has recently been reported, that is, efficient antibody production is induced by the conjugation of antigen and adjuvant. In this study, we aimed to develop a self-adjuvanting vaccine that can maximize the adjuvant effect of lipid A by conjugating lipid A with antigens while retaining its immunostimulatory properties. We developed a strategy to mimic the natural structure and successfully synthesized a conjugate of lipid A with Tn antigen via a sugar chain mimic linker, and it was confirmed that the synthesized conjugate retain lipid A’s innate immunostimulatory properties.
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| Academic Significance and Societal Importance of the Research Achievements |
昨今の新型コロナウイルス感染症の蔓延を契機に、我々の生活様式は大きく変化し、ワクチン開発研究はより一層大きな注目を集めている。ワクチンアジュバントとして有望視されている免疫活性化因子リピドAの高次機能化を目的とした本研究の成果は、革新的ワクチン開発のシーズであり、大きな社会貢献が期待できる。また、リピドAを基盤とした自然-獲得免疫制御分子の創製は、合成化学分野と免疫学分野の双方に学術的貢献が可能であり、非常に意義深いものであると考えている。
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Report
(4 results)
Research Products
(108 results)
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[Journal Article] α‐Emitting cancer therapy using 211 At‐AAMT targeting LAT12021
Author(s)
Kaneda‐Nakashima Kazuko、Zhang ZiJian、Manabe Yoshiyuki、Shimoyama Atsushi、Kabayama Kazuya、Watabe Tadashi、Kanai Yoshikatsu、Ooe Kazuhiro、Toyoshima Atsushi、Shirakami Yoshifumi、Yoshimura Takashi、Fukuda Mitsuhiro、Hatazawa Jun、Nakano Takashi、Fukase Koichi、Shinohara Atsushi
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Journal Title
Cancer Science
Volume: 112
Issue: 3
Pages: 1132-1140
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Activation of MyD88- and TRIF-mediated Signaling Pathways by Alcaligenes Lipid A for Efficient Antigen Presentation and T Cell Differentiation by Dendritic Cells2022
Author(s)
Xiao Sun, Koji Hosomi, Atsushi Shimoyama, Ken Yoshii, Zilai Liu, Huangwenxian Lan, Yunru Wang, Haruki Yamaura, Davie Kenneth, Azusa Saika, Takahiro Nagatake, Ken J. Ishii, Shizuo Akira, Hiroshi Kiyono, Koichi Fukase, and Jun Kunisawa
Organizer
2022 ISV ANNUAL CONGRESS
Related Report
Int'l Joint Research
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[Presentation] Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine2022
Author(s)
Zilai Liu, Koji Hosomi, Atsushi Shimoyama, Ken Yoshii, Xiao Sun, Huangwenxian Lan, Yunru Wang, Haruki Yamaura, Davie Kenneth, Azusa Saika, Takahiro Nagatake, Hiroshi Kiyono, Koichi Fukase, Jun Kunisawa
Organizer
2022 ISV ANNUAL CONGRESS
Related Report
Int'l Joint Research
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[Presentation] Activation of MyD88- and TRIF-mediated Signaling Pathways by Alcaligenes Lipid A for Efficient Antigen Presentation and T Cell Differentiation by Dendritic Cells2022
Author(s)
Xiao Sun, Koji Hosomi, Atsushi Shimoyama, Ken Yoshii, Haruki Yamaura, Davie Kenneth, Azusa Saika, Takahiro Nagatake, Hiroshi Kiyono, Koichi Fukase, and Jun Kunisawa
Organizer
第51回日本免疫学会学術総会
Related Report
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[Presentation] Adjuvant Activity of Chemically Synthesized Alcaligenes Lipid A to Augment Immune Responses against Haemophilus Influenzae Type B Conjugate Vaccine2022
Author(s)
Zilai Liu, Koji Hosomi, Atsushi Shimoyama, Ken Yoshii, Xiao Sun, Huangwenxian Lan, Yunru Wang, Haruki Yamaura, Davie Kenneth, Azusa Saika, Takahiro Nagatake, Hiroshi Kiyono, Koichi Fukase, Jun Kunisawa
Organizer
第51回日本免疫学会学術総会
Related Report
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[Presentation] リピドAを介した細菌-宿主間ケミカルエコロジーの理解とワクチンアジュバント開発への展開2021
Author(s)
下山敦史, 山浦遼生, 宇戸智哉, Davie Kenneth, 松田彩那, 細見 晃司, Di Lorenzo Flaviana, 藤本ゆかり, Molinaro Antonio, 國澤純, 清野宏, 深瀬浩一
Organizer
新学術領域研究「化学コミュニケーションのフロンティア」第８回公開シンポジウム
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