Establishment of an innovative vaccine platform with self-adjuvant function

• Project/Area Number: 26460560
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Saitama Medical University
• Principal Investigator: MATSUI Masanori 埼玉医科大学, 医学部, 准教授 (50199741)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: ワクチン / ウイルス様粒子 / ナノキャリア / アジュバント / ドラッグデリバリー / 細胞傷害性T細胞 / HLA class I / SV40 / 抗原提示関連分子 / VLP

Outline of Final Research Achievements

When mice were immunized with antigenic epitope-inserted virus like particles (VLP) prepared from SV40, epitope-specific cytotoxic T cells (CTL) can be induced efficiently without adding an artificial adjuvant. Therefore, the self-adjuvant activity that activates innate immunity is considered to exist in VLP itself. In this study, I attempted to elucidate the mechanism of this self-adjuvant function using various approaches. Then, we identified molecules that showed a change in expression level by stimulation of VLP. VLP was also effective for mucosal immunity. Furthermore, it was shown that CTL can be efficiently induced by various CTL epitopes. These data indicate that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties.

Research Products

• [Journal Article] Characterization of the flow cytometric assay for ex vivo monitoring of cytotoxicity mediated by antigen-specific cytotoxic T lymphocytes. (2017)
  • Author(s): Takagi, A., Y. Horiuchi, and M. Matsui.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 492 Issue: 1 Pages: 27-32
  • DOI: 10.1016/j.bbrc.2017.08.045
  • Peer Reviewed / Open Access
• [Journal Article] SV40 VP1 major capsid protein in its self-assembled form allows VP1 pentamers to coat various types of artificial beads in vitro regardless of their sizes and shapes. (2015)
  • Author(s): Kawano M., K. Doi, H. Fukuda, Y. Kita, K. Imai, T. Inoue, T. Enomoto, M. Matsui, M. Hatakeyama, Y. Yamaguchi, and H. Handa.
  • Journal Title: Biotechnol. Rep. Volume: 5 Pages: 105-111
  • Peer Reviewed
• [Journal Article] Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants (2014)
  • Author(s): M.-A. Kawano, K. Morikawa, T. Suda, N. Ohno, S. Matsushita, T. Akatsuka, H. Handa, M. Matsui
  • Journal Title: Virology Volume: 448 Pages: 159-167
  • DOI: 10.1016/j.virol.2013.10.010
  • Peer Reviewed
• [Journal Article] Introduction of a point mutation into an HLA class I single-chain trimer induces enhancement of CTL priming and antitumor immunity. (2014)
  • Author(s): Matsui, M., M. Kawano, S. Matsushita, and T. Akatsuka.
  • Journal Title: Molecular Therapy - Methods & Clinical Development Volume: 1 Pages: 1-11
  • DOI: 10.1038/mtm.2014.27
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Development of universal HCV vaccine by coupling HCV NS3 protein to the surface of liposomes. (2015)
  • Author(s): Takagi A., N. Kobayashi, M. Matsui, Y. Horiuchi, and T. Akatsuka.
  • Organizer: 第44回日本免疫学会
  • Place of Presentation: 北海道、札幌コンベンションセンター
  • Year and Date: 2015-11-18
• [Presentation] Development of universal HCV vaccinie by coupling HCV NS3 proteins to the surface of liposomes. (2015)
  • Author(s): Takagi, A., Kobayashi, N., Matsui, M., Horiuchi, Y., Kumar, A., and Akatsuka, T.
  • Organizer: International Symposium on Hepatitis C virus and related viruses
  • Place of Presentation: フランス、ストラスバーグ
  • Year and Date: 2015-10-09
• [Presentation] HLA-A2 mutantからなるSingle-chain trimerによるペプチド特異的細胞傷害性T細胞の誘導増強効果 (2015)
  • Author(s): 松井政則、川野雅章、松下祥、赤塚俊隆
  • Organizer: 第26回日本生体防御学会総会
  • Place of Presentation: 東京、台東区生涯学習センター
  • Year and Date: 2015-07-10
• [Presentation] Characterization of an HLA class I molecule with a point mutation that enhances the presentation of an exogenously loaded peptide but fails to present an endogenous peptide. (2014)
  • Author(s): Masanori Matsui, Masaaki Kawano, Sho Matsushita, and Toshitaka Akatsuka
  • Organizer: 第43回 日本免疫学会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] HLA-A2 mutantからなる Single-chain trimerによる抗腫瘍免疫誘導の増強 (2014)
  • Author(s): 松井政則 、川野雅章、松下祥、赤塚俊隆
  • Organizer: 第18回 日本がん免疫学会
  • Place of Presentation: ひめぎんホール（愛媛県松山市）
  • Year and Date: 2014-07-30 – 2014-08-01
• [Presentation] 細胞傷害性T細胞誘導剤によるがんCTLエピトープに対するCTLの誘導 (2014)
  • Author(s): 川野雅章、松下祥、赤塚俊隆、半田宏、松井政則
  • Organizer: 第18回 日本がん免疫学会
  • Place of Presentation: ひめぎんホール（愛媛県松山市）
  • Year and Date: 2014-07-30 – 2014-08-01