Development of Highly Functionalized Lipid A and its Application to Innate and Acquired Immune Regulatory Molecules

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K05749
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Osaka University
• Principal Investigator: Shimoyama Atsushi 大阪大学, 大学院理学研究科, 助教 (90625055)
• Project Period (FY): 2020-04-01 – 2023-03-31
• 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

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.

Free Research Field

ケミカルバイオロジー

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。