• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of a screening system of novel antigenic variants using a low-fidelity polymerase-based influenza virus strain.

Research Project

Project/Area Number 17K09170
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hygiene and public health
Research InstitutionKawasaki Medical School

Principal Investigator

Naito Tadasuke  川崎医科大学, 医学部, 講師 (50455937)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsインフルエンザウイルス / ワクチン開発 / 抗原変異 / ウイルスポリメラーゼ / 遺伝子変異 / 免疫逃避 / ウイルスライブラリー / ウイルス進化 / ウィルス / 感染症 / 免疫学 / 衛生
Outline of Final Research Achievements

Influenza A virus rapidly acquires antigenic changes, which limit the effectiveness of vaccines, primarily owing to its high rate of evolution. To predict the antigenic properties of future epidemic strains of human influenza A virus, we attempted to develop the screening system of novel antigenic variants using a mutator polymerase-based influenza virus strain. An important advantage of our method for isolation of an escape variant is that we can screen those viruses using the mutant virus library derived from own low-fidelity polymerase that do not require random mutagenesis by targeting PCR.
In this study, we demonstrated that antigenic escape variants could be isolated from mutant virus libraries with random mutations introduced by RNA genome-wide mutagenesis system for the whole influenza viral gene. This approach would enable the selection of future vaccine candidates before antigenic mutant viruses emerge in nature.

Academic Significance and Societal Importance of the Research Achievements

ワクチン製造株の選定条件として、①ウイルス増幅時に抗原部位に変異が導入されず、②ウイルスが高増殖性であり、③ウイルス抗原蛋白質(ヘマグルチニン)が高収率で精製できる必要がある。新規抗原変異株の出現後に、以上の条件を備えたウイルス株を速やかに単離して次シーズンのワクチン製造に間に合わせるのは困難である。本研究により、単離した抗原変異株のウイルス学的特徴と将来的なウイルス進化の方向性を事前に把握できれば、新規抗原変異株の出現時において迅速なワクチン開発が可能になる。さらに、その情報をもとに「未来流行株」に対するワクチン製造プロトコルを確立することが可能になる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (16 results)

All 2020 2019 2018 2017 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (7 results) (of which Int'l Joint Research: 1 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] EOS, an Ikaros family zinc finger transcription factor, interacts with the HTLV-1 oncoprotein Tax and is downregulated in peripheral blood mononuclear cells of HTLV-1-infected individuals, irrespective of clinical statuses.2019

    • Author(s)
      Naito T, Ushirogawa H, Fukushima T, Tanaka Y, Saito M.
    • Journal Title

      Virology Journal

      Volume: 16 Issue: 1 Pages: 160-160

    • DOI

      10.1186/s12985-019-1270-1

    • NAID

      120006937799

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tyr82 Amino Acid Mutation in PB1 Polymerase Induces an Influenza Virus Mutator Phenotype2019

    • Author(s)
      Naito Tadasuke、Shirai Kazumasa、Mori Kotaro、Muratsu Hidetaka、Ushirogawa Hiroshi、Ohniwa Ryosuke L.、Hanada Kousuke、Saito Mineki
    • Journal Title

      Journal of Virology

      Volume: 93 Issue: 22

    • DOI

      10.1128/jvi.00834-19

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distinct gene expression signatures induced by viral transactivators of different HTLV-1 subgroups that confer a different risk of HAM/TSP.2018

    • Author(s)
      Naito T, Yasunaga JI, Mitobe Y, Shirai K, Sejima H, Ushirogawa H, Tanaka Y, Nakamura T, Hanada K, Fujii M, Matsuoka M, Saito M.
    • Journal Title

      Retrovirology

      Volume: 15 Issue: 1 Pages: 72-72

    • DOI

      10.1186/s12977-018-0454-x

    • NAID

      120006847301

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The CC chemokine ligand (CCL) 1, upregulated by the viral transactivator Tax, can be downregulated by minocycline: possible implications for long-term treatment of HTLV-1-associated myelopathy/tropical spastic paraparesis2017

    • Author(s)
      Saito Mineki、Sejima Hiroe、Naito Tadasuke、Ushirogawa Hiroshi、Matsuzaki Toshio、Matsuura Eiji、Tanaka Yuetsu、Nakamura Tatsufumi、Takashima Hiroshi
    • Journal Title

      Virology Journal

      Volume: 14 Issue: 1 Pages: 234-234

    • DOI

      10.1186/s12985-017-0902-6

    • NAID

      120006849689

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevalence of plasma autoantibody against cancer testis antigen NY-ESO-1 in HTLV-1 infected individuals with different clinical status2017

    • Author(s)
      Shiohama Yasuo、Naito Tadasuke、Matsuzaki Toshio、Tanaka Reiko、Tomoyose Takeaki、Takashima Hiroshi、Fukushima Takuya、Tanaka Yuetsu、Saito Mineki
    • Journal Title

      Virology Journal

      Volume: 14 Issue: 1 Pages: 130-130

    • DOI

      10.1186/s12985-017-0802-9

    • NAID

      120006849690

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 低忠実性インフルエンザ株の性状解析とワクチン開発研究への応用2020

    • Author(s)
      内藤 忠相、齊藤 峰輝
    • Organizer
      9th Negative Strand Virus-Japan
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新規インフルエンザウイルスMutator株を用いた変異ウイルスライブラリー作出技術の開発2019

    • Author(s)
      内藤 忠相
    • Organizer
      BioJapan2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] インフルエンザウイルスの未来流行株予測システムの開発2018

    • Author(s)
      内藤 忠相
    • Organizer
      科学技術振興機構 ライフサイエンス 新技術説明会
    • Related Report
      2018 Research-status Report
  • [Presentation] 複製エラーが入りやすい低忠実性インフルエンザウイルス変異株の単離と性状解析2018

    • Author(s)
      内藤 忠相、齊藤 峰輝
    • Organizer
      第33回中国四国ウイルス研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] インフルエンザウイルスのゲノム複製忠実度を制御するポリメラーゼ機能部位の同定2018

    • Author(s)
      内藤 忠相、齊藤 峰輝
    • Organizer
      7th Negative Strand Virus-Japan
    • Related Report
      2017 Research-status Report
  • [Presentation] HAM発症リスクに関連するHTLV-1遺伝子型特異的な宿主遺伝子の発現制御メカニズムの解析2017

    • Author(s)
      内藤 忠相、齊藤 峰輝
    • Organizer
      第4回日本HTLV-1学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Development of high-fidelity influenza A virus vaccine strain2017

    • Author(s)
      Tadasuke Naito, Hiroshi Ushirogawa, and Mineki Saito
    • Organizer
      17th International Congress of Virology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] 川崎医科大学 微生物学教室 ホームページ

    • URL

      http://www.kawasaki-m.ac.jp/microbiology/

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
  • [Remarks] 川崎医科大学微生物学教室ホームページ

    • URL

      http://www.kawasaki-m.ac.jp/microbiology/

    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] インフルエンザウイルスRNAポリメラーゼの変異型PB12018

    • Inventor(s)
      内藤 忠相、齊藤 峰輝
    • Industrial Property Rights Holder
      学校法人 川崎学園
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] インフルエンザウイルスRNAポリメラーゼの変異型PB12017

    • Inventor(s)
      内藤 忠相、齊藤 峰輝
    • Industrial Property Rights Holder
      学校法人 川崎学園
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-214983
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi