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New rotavirus vaccine platforms using reverse genetics systems

Research Project

Project/Area Number 18H02663
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49060:Virology-related
Research InstitutionOsaka University

Principal Investigator

Kobayashi Takeshi  大阪大学, 微生物病研究所, 教授 (90324847)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2020: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywordsワクチン / ロタウイルス / リバースジェネティクス系
Outline of Final Research Achievements

Rotaviruses are a major cause of severe gastroenteritis in infants and young children worldwide and are responsible for approximately 215,000 deaths annually, particularly in developing countries. The objective of this research is to understand how rotaviruses replicate in vitro and cause diseases in vivo using plasmid-based rotavirus reverse genetics systems. We established a plasmid-based reverse genetics system for G4P[8] human rotavirus strain Odelia. Using reverse genetics systems, we recovered a panel of monoreassortant viruses harboring one gene segment from strain Odelia within the simian rotavirus strain SA11 genetic backbone. We also tried to develop a reverse genetics system for murine rotavirus strain EW. Reassortant viruses between strains SA11 and EW generated by the rescue system enabled study of the biological functions of viral gene segments. These systems will provide insight into the molecular mechanisms underlying rotavirus replication and pathogenesis.

Academic Significance and Societal Importance of the Research Achievements

現在、使用されているロタウイルスワクチンにおいては、発展途上国における不十分な防御効果、高額な費用、副反応(腸重積症)等の問題があげられており、次世代ワクチンの開発研究は重要な課題である。これまで有用なリバースジェネティクス系の開発の遅れからロタウイルスの複製機構ならびに病態発現機序の解明は進んでいなかった。本研究成果で開発されたヒトおよびマウスロタウイルス株のリバースジェネティクス系やレポーター遺伝子発現ロタウイルスを用いた研究は新規ワクチン開発や感染伝播、病態発現機序の理解につながると期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (28 results)

All 2021 2020 2019 2018

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (17 results) (of which Int'l Joint Research: 6 results,  Invited: 3 results) Book (3 results)

  • [Journal Article] Reverse Genetics Approach for Developing Rotavirus Vaccine Candidates Carrying VP4 and VP7 Genes Cloned from Clinical Isolates of Human Rotavirus2021

    • Author(s)
      Kanai Y, Onishi M, Kawagishi T, Pimfhun P, Nurdin J, Nouda R, Yamasaki M, Tina L, Pattara K, Okitsu S, Hayakawa S, Ebina H, Ushijima H, Kobayashi T
    • Journal Title

      Journal of Virology

      Volume: 95 Issue: 2

    • DOI

      10.1128/jvi.01374-20

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Generation of recombinant rotaviruses encoding a split NanoLuc peptide tag2021

    • Author(s)
      Pimfhun P, Kanai Y, Kawagishi T, Nouda R, Nurdin J, Yamasaki M, Nomura K, Tina L, Kobayashi T
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 534 Pages: 740-746

    • DOI

      10.1016/j.bbrc.2020.11.007

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Construction and characterization of an infectious clone generated from Chikungunya virus SL11131 strain2021

    • Author(s)
      Suzuki Y, Tanaka A, Maeda Y, Emi A, Fujioka Y, Sakaguchi S, SG Vasudevan, Kobayashi T , CK Lim, Takasaki T, H Wu, Nakano T
    • Journal Title

      Virology

      Volume: 552 Pages: 52-62

    • DOI

      10.1016/j.virol.2020.09.006

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Generation of Genetically RGD-Modified Oncolytic Reovirus That Enhances JAM-A-Independent Infection of Tumor Cells2020

    • Author(s)
      Kawagishi T, Kanai Y, Nouda R, Fukui I, Nurdin JA, Matsuura Y, Kobayashi T
    • Journal Title

      Journal of Virology

      Volume: 94 Issue: 23

    • DOI

      10.1128/jvi.01703-20

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reverse Genetics System for a Human Group A Rotavirus.2020

    • Author(s)
      Kawagishi T, Nurdin J, Onishi M, Nouda R, Kanai Y, Tajima T, Ushijima H, Kobayashi T
    • Journal Title

      J Virol

      Volume: 94 Issue: 2

    • DOI

      10.1128/jvi.00963-19

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cell-cell fusion induced by reovirus FAST proteins enhances replication and pathogenicity of non-enveloped dsRNA viruses.2019

    • Author(s)
      1.Kanai Y, Kawagishi T, Sakai Y, Nouda R, Shimojima M, Saijo M, Matsuura Y, Kobayashi T.
    • Journal Title

      PLoS Pathog.

      Volume: 15 Issue: 4 Pages: e1007675-e1007675

    • DOI

      10.1371/journal.ppat.1007675

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In Vivo Live Imaging of Oncolytic Mammalian Orthoreovirus Expressing NanoLuc Luciferase in Tumor Xenograft Mice2019

    • Author(s)
      Kanai Yuta、Kawagishi Takahiro、Matsuura Yoshiharu、Kobayashi Takeshi
    • Journal Title

      Journal of Virology

      Volume: 93 Issue: 14

    • DOI

      10.1128/jvi.00401-19

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of Stable Rotavirus Reporter Expression Systems2019

    • Author(s)
      Kanai Y, Kawagishi T, Nouda R, Onishi M, Pannacha P, Nurdin JA, Nomura K, Matsuura Y, Kobayashi T.
    • Journal Title

      Journal of Virology

      Volume: 93 Issue: 4

    • DOI

      10.1128/jvi.01774-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] ロタウイルス感染における多様な細胞表面糖鎖レセプターの意義2020

    • Author(s)
      山﨑 萌子、金井 祐太、浜島 りな、南 昌平、Pannacha Pimfhun、納田 遼太郎、Jeffry Nurdin、Tina Lusiany、松本 真依、大西 未紗、小林 剛
    • Organizer
      第163回日本獣医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Reverse Genetics System for a Human Group A Rotavirus2020

    • Author(s)
      Kawagishi T, Nurdin A, Onishi M, Nouda R, Kanai Y, Tajima T, Ushijima H, Kobayashi T.
    • Organizer
      U.S.-Japan Cooperative Medical Sciences Program's 22nd International Conference on Emerging Infectious Diseases in the Pacific Rim
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Application of Reverse Genetics Systems in Studies of dsRNA Virus Replication and Pathogenesis2019

    • Author(s)
      Kobayashi T.
    • Organizer
      Gordon Research Conference Viruses and Cells
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Reverse Genetic System for Human Rotavirus A Odelia strain2019

    • Author(s)
      Nurdin J, Kawagishi T, Onishi M, Kanai Y, Tajima T, Ushijima H, Kobayashi T.
    • Organizer
      The 18th Awaji International Forum on Infection and Immunity
    • Related Report
      2019 Annual Research Report
  • [Presentation] ロタウイルス NSP3タンパク質のeIF4G結合領域変異がウイルス複製に及ぼす影響2019

    • Author(s)
      納田遼太郎, 金井祐太, 川岸崇裕, Pannacha Pimfhun, 小林剛
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Reverse Genetic System for Human Rotavirus A Odelia strain2019

    • Author(s)
      Nurdin J, Kawagishi T, Onishi M, Kanai Y, Tajima T, Ushijima H, Kobayashi T.
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ロタウイルスベクターの開発2019

    • Author(s)
      金井祐太, 川岸崇裕, Pannacha Pimfhun , 納田遼太郎, 大西未沙, Nurdin Jeffry, 野村圭一郎, Tina Luciany, 山﨑萌子, 小林剛
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ロタウイルス人工合成法の開発と新規ワクチン2018

    • Author(s)
      Kobayashi T.
    • Organizer
      第22回日本ワクチン学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Nelson Bay reovirus σC body domain is associated with strain-specific differences in viral replication2018

    • Author(s)
      Kawagishi T, Kanai Y, Sakai Y, Nouda R, Tani H, Shimojima M, Saijo M, Matsuura Y, Kobayashi T.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Platform for rotavirus vaccine development using plasmid-based reverse genetics2018

    • Author(s)
      Kanai Y, Kawagishi T, Onishi M, Pannacha P, Nouda R, Nurdin J, Nomura K, Ushijima H, Kobayashi T.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Fusogenic bat-borne orthoreovirus p17 protein regulates viral replication in a host-specific manner2018

    • Author(s)
      Nouda R, Kawagishi T, Kanai Y, Shimojima M, Saijo M, Matsuura Y, Kobayashi T.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of stable reporter rotaviruses2018

    • Author(s)
      Pannacha P, Kanai Y, Onishi M, Kawagishi T, Nouda R, Nurdin J, Matsuura Y, Kobayashi T.
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Reverse genetics systems for orthoreoviruses and rotaviruses2018

    • Author(s)
      Kobayashi T.
    • Organizer
      13th International dsRNA Symposium 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Antigenicity of simian and human reassortant rotaviruses generated by reverse genetics2018

    • Author(s)
      Kanai Y, Kawagishi T, Onishi M, Pannacha P, Nouda R, Nurdin J, Nomura K, Ushijima H, Kobayashi T.
    • Organizer
      13th International dsRNA Symposium 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nelson Bay Orthoreovirus cell attachment protein σC determines strain-specific differences in viral replication and pathogenesis2018

    • Author(s)
      Kawagishi T, Kanai Y, Yusuke Sakai, Nouda R,Tani H, Shimojima M, Saijo M, Matsuura Y, Kobayashi T.
    • Organizer
      13th International dsRNA Symposium 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 次世代組換えロタウイルスワクチン作製の試み2018

    • Author(s)
      金井 祐太、川岸 崇裕、Pimfhun Pannacha、納田 遼太郎、Nurdin Jeffery、野村 圭一郎、牛島 廣治、小林 剛
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Nelson Bay orthoreovirus p17 protein regulates viral replication in a host-specific manner2018

    • Author(s)
      Kobayashi T.
    • Organizer
      第12回日中国際ウイルス学会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Book] Pharama Medica January 2021 vol.39 No12021

    • Author(s)
      南 昌平、小林 剛
    • Total Pages
      6
    • Publisher
      メディカルレビュー社
    • ISBN
      9784779224621
    • Related Report
      2020 Annual Research Report
  • [Book] 腎と透析2018

    • Author(s)
      小林 剛
    • Total Pages
      3
    • Publisher
      東京医学社
    • Related Report
      2018 Annual Research Report
  • [Book] 獣医畜産新報2018

    • Author(s)
      川岸 崇裕
    • Total Pages
      7
    • Publisher
      文永堂出版
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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