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Development of VLP vaccines using protein-protein self-joining system

Research Project

Project/Area Number 20K07524
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49060:Virology-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

TAKEUCHI Kaoru  筑波大学, 医学医療系, 准教授 (00192162)

Co-Investigator(Kenkyū-buntansha) 中平 洋一  茨城大学, 農学部, 准教授 (40423868)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsウイルス様中空粒子 / VLP / BVDV / RGNNV / SpyTag/SpyCatcher / 牛下痢症ウイルス / キジハタ神経壊死ウイルス / ワクチン / 大腸菌 / バキュロウイルス / マウス / 経口ワクチン / 経鼻ワクチン / 植物
Outline of Research at the Start

ウイルス様中空粒子(Virus-like particles: VLP)は、ウイルスの外殻タンパク質によって構築された構造体でありゲノムを持たないため感染性がなく安全性が高い。しかも、外殻タンパク質の繰り返し構造からなるため強い免疫原性を示す。本研究では、大腸菌あるいは植物葉緑体で発現させた魚病ウイルス(RGNNV)のVLPに抗原となる病原ウイルスの膜タンパク質等を高密度で付加し、さまざまな疾病の予防に役立つ汎用性の高い経口あるいは経鼻用ワクチンプラットフォームの開発を目指す。

Outline of Final Research Achievements

Bovine viral diarrhea virus (BVDV) is a pathogen of commercial consequence in cattle. Although many vaccines are commercially available, their drawbacks precipitate the need for new effective vaccines. Virus-like particles (VLPs) are safe and powerful technology; however, it is difficult to produce large amounts of BVDV VLP. In this study, we generated red-spotted grouper nervous necrosis virus (RGNNV) VLP presenting BVDV E2 protein by exploiting SpyTag/SpyCatcher technology. Mice immunized with RGNNV VLP conjugated with E2 proteins of Nose and KZ-91-CP strains at day 0 and 14 elicited robust IgG titers against E2 proteins of homologous strains. In addition, this prime-boost regimen induced strong neutralization titers against homologous BVDV strains. Our results indicate that conjugation of E2 protein to RGNNV VLP strongly enhanced the antigenicity of E2 protein and that RGNNV VLPs presenting E2 protein are promising BVDV vaccine candidates.

Academic Significance and Societal Importance of the Research Achievements

BVDVは牛ウイルス性下痢・粘膜病を引き起こす重要な病原体で、畜産業に甚大な経済損失をもたらしている。現在、BVDVに対する治療法はなく、感染牛の摘発淘汰またはワクチンによる予防が有効な対策とされている。しかし、現行の生ワクチンは、妊娠牛への接種により胎内感染が起こるため接種ができないという問題がある。また不活化ワクチンは、抗体価が低く予防効果が完全ではないという課題がある。本研究で作成したE2抗原を提示するVLPワクチンは有望なワクチン候補と考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2023 2021 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Remarks (1 results)

  • [Journal Article] Novel bovine viral diarrhea virus (BVDV) virus-like particle vaccine candidates presenting the E2 protein using the SpyTag/SpyCatcher system induce a robust neutralizing antibody response in mice2023

    • Author(s)
      Katsura M, Fukushima M, Kameyama KI, Kokuho T, Nakahira Y, Takeuchi K
    • Journal Title

      Arch Virol

      Volume: 168 Issue: 2 Pages: 49-58

    • DOI

      10.1007/s00705-022-05653-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of a photocontrollable recombinant bovine parainfluenza virus type 32023

    • Author(s)
      Okura T, Tahara M, Otsuki N, Sato M, Takeuchi K, Takeda M.
    • Journal Title

      Microbiol Immunol

      Volume: 67 Issue: 4 Pages: 204-209

    • DOI

      10.1111/1348-0421.13052

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mass Production of Virus-Like Particles Using Chloroplast Genetic Engineering for Highly Immunogenic Oral Vaccine Against Fish Disease.2021

    • Author(s)
      Nakahira Y, Mizuno K, Yamashita H, Tsuchikura M, Takeuchi K, Shiina T, Kawakami H
    • Journal Title

      Front Plant Sci.

      Volume: 12 Pages: 717952-717952

    • DOI

      10.3389/fpls.2021.717952

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Remarks] (プレスリリース)養殖魚の疾病予防に有効な「食べるワクチン」を葉緑体工学で開発

    • URL

      https://www.tsukuba.ac.jp/journal/pdf/p202108231300.pdf

    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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