Vaccine development against tuberculosis and AIDS by the use of lipid immunity

• Project/Area Number: 18H02852
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Kyoto University
• Principal Investigator: Sugita Masahiko 京都大学, ウイルス・再生医科学研究所, 教授 (80333532)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2020: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: リポペプチド / MHC / 脂質免疫 / ワクチン / 結核 / エイズ

Outline of Final Research Achievements

Recent evidence indicated that lipopeptides comprise a novel class of antigen recognized by T cells. We aimed at elucidating how this immune pathway functions and establishing valuable small animal models that are suitable for lipopeptide immunity research, hoping to contribute to the development of new type of vaccines. Indeed, we were able to establish murine models equipped with the ability to respond to lipopeptides when sensitized with lipopeptide-loaded BCG vaccines. Therefore, this study served to construct an important basis for developing a new type of lipopeptide vaccines.

Academic Significance and Societal Importance of the Research Achievements

ウイルスリポペプチドを標的とした新しい免疫応答がどのようにして起きるのか、そのメカニズムを明らかにしました。またリポペプチド免疫を起こりやすくしたマウスモデルを樹立し、どのようにリポペプチドを接種すればリポペプチド特異的免疫応答が効率的に惹起できるのか、その方法を発見しました。これらの成果は、リポペプチドを主体とした新しいタイプのワクチン開発へと結実する可能性があります。

Research Products

• [Journal Article] Crystal structure of the ternary complex of TCR, MHC class I and lipopeptides. (2020)
  • Author(s): Morita D, Iwashita C, Mizutani T, Mori N, Mikami B, Sugita M.
  • Journal Title: International Immunology Volume: 32 Issue: 12 Pages: 805-810
  • DOI: 10.1093/intimm/dxaa050
  • Peer Reviewed
• [Journal Article] Crystal structures of lysophospholipid-bound MHC class I molecules (2020)
  • Author(s): Shima Yoko、Morita Daisuke、Mizutani Tatsuaki、Mori Naoki、Mikami Bunzo、Sugita Masahiko
  • Journal Title: Journal of Biological Chemistry Volume: in press Issue: 20 Pages: 6983-6991
  • DOI: 10.1074/jbc.ra119.011932
  • Peer Reviewed
• [Journal Article] Identification and Structure of an MHC Class I-Encoded Protein with the Potential to Present N-Myristoylated 4-mer Peptides to T Cells (2019)
  • Author(s): Yamamoto Y, Morita D, Shima Y, Midorikawa A, Mizutani T, Suzuki J, Mori N, Shiina T, Inoko H, Tanaka Y, Mikami B, Sugita M.
  • Journal Title: Journal of Immunology Volume: 202 Issue: 12 Pages: 3349-3358
  • DOI: 10.4049/jimmunol.1900087
  • Peer Reviewed
• [Presentation] 霊長類研究から見えてきた、非ペプチド抗原を標的とする新しい獲得免疫機構 (2018)
  • Author(s): 森田大輔、嶋燿子、杉田昌彦
  • Organizer: 第29回日本生体防御学会学術総会
  • Invited
• [Presentation] リポペプチドを提示するMHC class 1 分子の内因性リガンドの同定 (2018)
  • Author(s): 嶋燿子、森田大輔、杉田昌彦
  • Organizer: 第29回日本生体防御学会学術集会
• [Presentation] 肉芽腫形成を制御するS100A9 (2018)
  • Author(s): 水谷龍明、吉岡佑弥、杉田昌彦
  • Organizer: 第29回日本生体防御学会学術総会
• [Remarks] MHCクラス1分子・リポペプチド・T細胞受容体複合体のX線結晶構造の解明
  • URL: https://www.infront.kyoto-u.ac.jp/achievements/post-6233/
• [Remarks] リポペプチド提示MHCクラス1分子の内因性リガンドを同定し、複合体のX線結晶構造を解明
  • URL: https://www.infront.kyoto-u.ac.jp/achievements/post-5362/
• [Remarks] 京大ウイルス研・杉田研究室
  • URL: https://www.infront.kyoto-u.ac.jp/ex_ivr/Lab/SugitaLab.html