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Characterization of immune activation and induction of adaptive immune responses by simian virus 40 virus-like particles

Research Project

Project/Area Number 19K07201
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionSaitama Medical University

Principal Investigator

Kawano Masaaki  埼玉医科大学, 医学部, 准教授 (30447528)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsPolyomavirus / Simian virus 40 / VP1 / Virus-like particle / Adjuvant / Adaptive immune response / Antibody production / Cell-mediated immunity / Antigen presentation / Antigen / Incorporation / OVA / Cellular immune response / Humoral immune response / simian virus 40 / virus-like particle / immune response / innate immunity / adaptive immunity / cytotoxic T lymphocyte / antibody production / vaccine / polyomavirus / adjuvant
Outline of Research at the Start

サルのポリオーマウイルスのsimian Virus 40 (SV40) のウイルス様粒子 (VLP, virus-like particle) に対する免疫応答として、SV40 VLPに対する、ヘルパーT細胞、B細胞、natural killer細胞、細胞傷害性T細胞の各々の免疫細胞の免疫活性化を解析することで、SV40 VLPによる免疫活性化機構の概観が明らかになると期待される。この解析によって、SV40 VLPの免疫活性化の効率と強度が明確になるものと思われる。また、この解析によって、目的とする抗原を内包したSV40 VLPをワクチンとして利用することの妥当性が確立されるものと期待される。

Outline of Final Research Achievements

Simian virus 40 (SV40) is a monkey polyomavirus. The icosahedral capsid of SV40 is 50 nm in diameter and consists only of major capsid protein SV40 VP1. In this study, we prepared specific antigen incorporated SV40 VLPs (Virus-like particles) from insect cells using baculovirus vector and addressed cell-mediated immunity and antibody production against the incorporated antigens. We revealed that SV40 VLP could induce adaptive immune responses against incorporated antigens without inducing the inflammatory cytokines. In order to reveal the SV40 specific immune responses, we prepared empty SV40 VLP from insect cells and analyzed T-helper differentiation of SV40 VLP-treated naive CD4+ T cells and cytokine/chemokine production by SV40 VLP-treated B cells, CD8+ T cells, natural killer cells, and peritoneal macrophages. In order to reveal the precise molecular mechanism of the SV40 VLP specific immune responses, we also analyzed the cellular proteins that interact with the SV40 VLP.

Academic Significance and Societal Importance of the Research Achievements

外来抗原を内包したSimian virus 40 (SV40) のウイルス様粒子 (VLP, virus-like particle) をマウスに免疫すると、外来抗原に対して抗原賦活物質を加えることなくアラムアジュバントと同等の抗体産生を誘導し、また、古典的な不完全フロイントアジュバントによる細胞性免疫誘導よりも効率良く細胞性免疫を誘導することが判明した。また、SV40 VLPに特有の免疫活性化機構として、抗原提示活性化因子の発現上昇とケモカインの産生を誘導することを発見し、SV40 VLPと結合する細胞性因子も同定した。これらの結果は、新規の免疫活性化誘導法の開発に有用であると考えられる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (16 results)

All 2021 2020 2019

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (4 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (8 results) (of which Overseas: 4 results)

  • [Journal Article] Istradefylline, an adenosine A2a receptor antagonist, ameliorates neutrophilic airway inflammation and psoriasis in mice.2021

    • Author(s)
      Tokano M, Kawano M, Takagi R, Matsushita S.
    • Journal Title

      Clin. Exp. Neuroimmunol.

      Volume: 12 Issue: 4 Pages: 268-275

    • DOI

      10.1111/cen3.12658

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tannic acid, a dopamine receptor agonist, ameliorates periodontitis, atopic dermatitis and psoriasis in animal models.2021

    • Author(s)
      Takagi R, Kawano M, Sato T, Matsushita S.
    • Journal Title

      Curr. Trends Immunol.

      Volume: 22 Pages: 11-17

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tannic acid acts as an agonist of the dopamine D2L receptor, regulates immune responses, and ameliorates experimentally induced colitis in mice2020

    • Author(s)
      Kawano Masaaki、Saika Kikue、Takagi Rie、Matsui Masanori、Matsushita Sho
    • Journal Title

      Brain, Behavior, & Immunity - Health

      Volume: 5 Pages: 100071-100071

    • DOI

      10.1016/j.bbih.2020.100071

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of adaptive immune responses against antigens incorporated within the capsid of simian virus 402020

    • Author(s)
      Saika Kikue、Kato Masahiko、Sanada Hideaki、Matsushita Sho、Matsui Masanori、Handa Hiroshi、Kawano Masaaki
    • Journal Title

      Journal of General Virology

      Volume: 101 Issue: 8 Pages: 853-862

    • DOI

      10.1099/jgv.0.001445

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] アデノシン受容体を介した好中球性炎症制御2021

    • Author(s)
      川野 雅章, 戸叶 美枝子, 高木 理英, 松下 祥
    • Organizer
      第70回日本アレルギー学会学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] アデノシンはエフェクターCD4陽性T細胞に作用しIL-17産生を介して好中球性炎症を惹起する2021

    • Author(s)
      戸叶 美枝子, 松下 祥, 高木 理英, 川野 雅章
    • Organizer
      第70回日本アレルギー学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] アデノシンはTh17細胞の分化を誘導しアデノシンA2a受容体拮抗薬はEAEを制御する2021

    • Author(s)
      戸叶 美枝子, 松下 祥, 高木 理英, 川野 雅章
    • Organizer
      第33回日本神経免疫学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Extracellular adenosine induces hypersecretion of IL-17A by T-helper 17 cells through the adenosine A2a receptor to promote neutrophilic inflammation.2021

    • Author(s)
      Masaaki Kawano, Mieko Tokano, Rie Takagi, Toshimasa Yamamoto, Sho Matsushita
    • Organizer
      The 50th Annual Meeting of The Japanese Society for Immunology, 2021
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] アデノシンA2A受容体の活性化を抑制する組成物2021

    • Inventor(s)
      川野雅章、松下祥、高木理英、戸叶美枝子
    • Industrial Property Rights Holder
      川野雅章、松下祥、高木理英、戸叶美枝子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 播種性血管内凝固症候群の予防又は治療用組成物2021

    • Inventor(s)
      松下祥、川野雅章、 戸叶美枝子、高木理英
    • Industrial Property Rights Holder
      松下祥、川野雅章、 戸叶美枝子、高木理英
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-071128
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 播種性血管内凝固症候群の予防又は治療用組成物2021

    • Inventor(s)
      松下祥、川野雅章、 戸叶美枝子、高木理英、前崎繁文、樽本憲人
    • Industrial Property Rights Holder
      松下祥、川野雅章、 戸叶美枝子、高木理英、前崎繁文、樽本憲人
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] アデノシンA2A受容体を標的とする組成物2020

    • Inventor(s)
      松下祥、川野雅章、高木理英、戸叶美枝子
    • Industrial Property Rights Holder
      松下祥、川野雅章、高木理英、戸叶美枝子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] アデノシン産生酵素を標的とする組成物2020

    • Inventor(s)
      川野雅章、松下祥、高木理英、戸叶美枝子
    • Industrial Property Rights Holder
      川野雅章、松下祥、高木理英、戸叶美枝子
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-109854
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] アデノシン産生酵素を標的とする組成物2020

    • Inventor(s)
      川野雅章、松下祥、高木理英、戸叶美枝子
    • Industrial Property Rights Holder
      川野雅章、松下祥、高木理英、戸叶美枝子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] アデノシンA2A受容体の活性化を抑制する組成物2020

    • Inventor(s)
      川野雅章、松下祥、高木理英、戸叶美枝子
    • Industrial Property Rights Holder
      川野雅章、松下祥、高木理英、戸叶美枝子
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-148336
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] アデノシンA2A受容体を標的とする組成物2019

    • Inventor(s)
      松下 祥、川野 雅章、高木 理英、戸叶 美枝子
    • Industrial Property Rights Holder
      松下 祥、川野 雅章、高木 理英、戸叶 美枝子
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-195478
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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