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Elucidation of Pathogenesis and Development of Therapeutic Strategies for Severe Pneumonia Caused by MERS-CoV Using an Infected Animal Model

Research Project

Project/Area Number 19K08945
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Naoko Iwata  国立感染症研究所, 感染病理部, 主任研究官 (10360695)

Project Period (FY) 2019-04-01 – 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 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)
Keywords動物モデル / コロナウイルス / 治療法
Outline of Research at the Start

MERS-CoVの本来の病原性は軽度の風邪を起こす程度のものであり重症化するには宿主側かウイルス側、あるいはその両方に原因がある。そこで、感染動物モデルを用いて、宿主側(マウス側)あるいはウイルス側を変化させて、MERS-CoVの重症肺炎の機序を探る。最終的には重症かの原因を特定し、病原性の解明、治療薬の開発、治療法の解明につなげる。

Outline of Final Research Achievements

MERS-CoV, a respiratory infection, causes pneumonia that is more likely to be severe in people with underlying medical conditions. The mechanism underlying its severe progression remains unknown, and the development of treatments and vaccines is still in progress. In this study, we established a severe pneumonia model using transgenic (Tg) mice expressing MERS-CoV receptors to investigate the differences between severe progression and recovery, aiming to elucidate the underlying mechanisms. Since reports suggested that reduced type 1 and type 2 IFNs contributed to the severe disease, we administered anti-IFNAR1 and anti-IFNγ antibodies to Tg mice to reduce inflammation, and then attempted to infect them with MERS-CoV. The mice showed an effect on body weight change, but did not become severely ill. It was clear that other factors in addition to inflammation were necessary for severe disease.

Academic Significance and Societal Importance of the Research Achievements

本研究は、MERS-CoVの重症化メカニズムを解明し、感染制御や治療法の開発に貢献する学術的な意義がある。また、type 1およびtype 2 IFNの低下が重症化の要因と示唆され、炎症以外の要素も関与していることが明らかとなった。MERS-CoV感染症への理解が深まり、将来的な予防策や治療法の開発につながる可能性がある。これにより、感染症対策や公衆衛生政策の向上に貢献することが期待される。

Report

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

    (16 results)

All 2023 2022 2020 2019

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 6 results) Presentation (6 results)

  • [Journal Article] Specific COVID-19 risk behaviors and the preventive effect of personal protective equipment among healthcare workers in Japan2023

    • Author(s)
      Shimbashi Reiko、Ainai Akira、Iida Shun、Iwata-Yoshikawa Naoko、Sano Kaori、Yamada Souichi、Kuroda Yudai、Okuma Kazu、Nojima Kiyoko、Nagata Noriyo、Fukushi Shuetsu、Maeda Ken、Takahashi Yoshimasa、Suzuki Tadaki、Ohnishi Makoto、Tanaka-Taya Keiko
    • Journal Title

      Global Health & Medicine

      Volume: 5 Issue: 1 Pages: 5-14

    • DOI

      10.35772/ghm.2022.01060

    • ISSN
      2434-9186, 2434-9194
    • Year and Date
      2023-02-28
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Saturation time of exposure interval for cross-neutralization response to SARS-CoV-2: Implications for vaccine dose interval2023

    • Author(s)
      Miyamoto Sho、Shiwa-Sudo Nozomi、Iwata-Yoshikawa Naoko、Sakai Yusuke、Nagata Noriyo、Arashiro Takeshi、Ainai Akira、Moriyama Saya、Kishida Noriko、Watanabe Shinji、Nojima Kiyoko、Seki Yohei、Mizukami Takuo、Hasegawa Hideki、Ebihara Hideki、Fukushi Shuetsu、Suzuki Tadaki
    • Journal Title

      iScience

      Volume: 26 Issue: 5 Pages: 106694-106694

    • DOI

      10.1016/j.isci.2023.106694

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of Reinfection with SARS-CoV-2 Omicron Variants in Previously Infected Hamsters2023

    • Author(s)
      Shiwa-Sudo Nozomi、Sakai Yusuke、Iwata-Yoshikawa Naoko、Watanabe Shinji、Yamada Souichi、Kuroda Yudai、Yamamoto Tsukasa、Shirakura Masayuki、Fujisaki Seiichiro、Miyazaki Kaya、Miura Hideka、Nagata Shiho、Fukushi Shuetsu、Maeda Ken、Hasegawa Hideki、Suzuki Tadaki、Nagata Noriyo
    • Journal Title

      Journal of Virology

      Volume: 97 Issue: 1 Pages: 1-21

    • DOI

      10.1128/jvi.01366-22

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Results from a preclinical study in rodents and a Phase 1/2, randomized, double-blind, placebo-controlled, parallel-group study of COVID-19 vaccine S-268019-a in Japanese adults2023

    • Author(s)
      Sonoyama Takuhiro、Iwata Satoshi、Shinkai Masaharu、Iwata-Yoshikawa Naoko、Shiwa-Sudo Nozomi、Hemmi Takuya、Ainai Akira、Nagata Noriyo、Matsunaga Nobuaki、Tada Yukio、Homma Tomoyuki、Omoto Shinya、Yokokawa Shibata Risa、Igarashi Kenji、Suzuki Tadaki、Hasegawa Hideki、Ariyasu Mari
    • Journal Title

      Vaccine

      Volume: 41 Issue: 11 Pages: 1834-1847

    • DOI

      10.1016/j.vaccine.2022.12.025

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immune response and protective efficacy of the SARS-CoV-2 recombinant spike protein vaccine S-268019-b in mice2022

    • Author(s)
      Homma Tomoyuki、Nagata Noriyo、Iwata-Yoshikawa Naoko、Shiwa-Sudo Nozomi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 20861-20861

    • DOI

      10.1038/s41598-022-25418-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Essential role of TMPRSS2 in SARS-CoV-2 infection in murine airways2022

    • Author(s)
      Iwata-Yoshikawa N, Kakizaki M, Shiwa-Sudo N, Okura T, Tahara M, Fukushi S, Maeda K, Kawase M, Asanuma H, Tomita Y, Takayama I, Matsuyama S, Shirato K, Suzuki T, Nagata N, Takeda M.
    • Journal Title

      Nat Commun . 2

      Volume: 13 Issue: 1 Pages: 6100-6100

    • DOI

      10.1038/s41467-022-33911-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intranasal vaccination induced cross-protective secretory IgA antibodies against SARS-CoV-2 variants with reducing the potential risk of lung eosinophilic immunopathology2022

    • Author(s)
      Hemmi Takuya、Ainai Akira、Hashiguchi Takao、Tobiume Minoru、Kanno Takayuki、Iwata-Yoshikawa Naoko、Iida Shun、Sato Yuko、Miyamoto Sho、Ueno Akira、Sano Kaori、Saito Shinji、Shiwa-Sudo Nozomi、Nagata Noriyo、Tamura Koji、Suzuki Ryosuke、Hasegawa Hideki、Suzuki Tadaki
    • Journal Title

      Vaccine

      Volume: 40 Issue: 41 Pages: 5892-5903

    • DOI

      10.1016/j.vaccine.2022.08.049

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunogenicity and protective efficacy of SARS-CoV-2 recombinant S-protein vaccine S-268019-b in cynomolgus monkeys2022

    • Author(s)
      Hashimoto Masayuki、Nagata Noriyo、Iwata-Yoshikawa Naoko、Shiwa-Sudo Nozomi、Sakai Yusuke、Shirakura Masayuki、Kishida Noriko、Arita Tomoko、Suzuki Yasushi、Watanabe Shinji、Asanuma Hideki、Sonoyama Takuhiro、Suzuki Tadaki、Omoto Shinya、Hasegawa Hideki
    • Journal Title

      Vaccine

      Volume: 40 Issue: 31 Pages: 4231-4241

    • DOI

      10.1016/j.vaccine.2022.05.081

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-S1 MERS-COV IgY Specific Antibodies Decreases Lung Inflammation and Viral Antigen Positive Cells in the Human Transgenic Mouse Model2020

    • Author(s)
      Aymn T. Abbas, Sherif A. El-Kafrawy , Sayed Sartaj Sohrab, Ashraf A. Tabll, Ahmed M. Hassan , Naoko Iwata-Yoshikawa , Noriyo Nagata and Esam I. Azhar
    • Journal Title

      Vaccines

      Volume: 8(4) Issue: 4 Pages: 634-634

    • DOI

      10.3390/vaccines8040634

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Gold nanoparticle-adjuvanted S protein induces a strong antigen-specific IgG response against severe acute respiratory syndrome-related coronavirus infection, but fails to induce protective antibodies and limit eosinophilic infiltration in lungs.2019

    • Author(s)
      Hanako Sekimukai, Naoko Iwata-Yoshikawa, Shuetsu Fukushi, Hideki Tani, Michiyo Kataoka, Tadaki Suzuki, Hideki Hasegawa, Kenichi Niikura, Katsuhiko Arai, Noriyo Nagata.
    • Journal Title

      Microbiology and Immunology

      Volume: 64 Issue: 1 Pages: 33-51

    • DOI

      10.1111/1348-0421.12754

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] マウスモデルを用いたSARS-CoV-2感染におけるTMPRSS2の役割についての解析.2022

    • Author(s)
      岩田 (吉河) 奈織子, 柿崎正敏, 志和 希, 大倉 喬, 田原舞乃, 福士秀悦, 前田 健, 川瀬みゆき, 冨田有里子, 高山郁代, 松山州徳, 白戸憲也, 鈴木忠樹, 竹田 誠, 永田典代.
    • Organizer
      第69回日本ウイルス学会 (長崎)
    • Related Report
      2022 Annual Research Report
  • [Presentation] 新型コロナウイルス既感染ハムスターにおけるオミクロン株再感染の可能性.2022

    • Author(s)
      志和(須藤)希、渡邉真治、岩田(吉河)奈織子、坂井祐介、長谷川秀樹、鈴木忠樹、永田典代.
    • Organizer
      第69回日本ウイルス学会 (長崎)
    • Related Report
      2022 Annual Research Report
  • [Presentation] SARS-CoV-2 の懸念される変異株 (VOCs) の性質解析.2022

    • Author(s)
      柿崎正敏、岩田 (吉河) 奈織子, 志和 希, 大倉 喬, 田原舞乃, 福士秀悦, 前田 健, 冨田有里子, 高山郁代, 松山州徳, 白戸憲也, 鈴木忠樹, 永田典代、竹田 誠.
    • Organizer
      第69回日本ウイルス学会 (長崎)
    • Related Report
      2022 Annual Research Report
  • [Presentation] ODN2006をアジュバントとする経鼻COVID-19ワクチンは広域中和能を有するIgA抗体を誘導し、ワクチン関連呼吸器疾患増強のリスクを軽減できる.2022

    • Author(s)
      逸見拓矢、相内章、橋口隆生、飛梅実、菅野隆行、岩田(吉河)奈織子、飯田俊、佐藤由子、宮本翔、上野朗、佐野芳、齋藤慎二、志和(須藤)希、永田典代、田村浩二、鈴木亮介、長谷川秀樹、鈴木忠樹.
    • Organizer
      第69回日本ウイルス学会 (長崎)
    • Related Report
      2022 Annual Research Report
  • [Presentation] SARS-CoV-2変異株の猫における病原性比較.2022

    • Author(s)
      朴ウンシル、黒田雄大、加来義浩、奥谷晶子、立本完吾、石嶋慧多、堀田明豊、井上雄介、原田倫子、網 康至、宇田晶彦、原田俊彦、志和 希、坂井祐介、岩田奈織子、永田典代、鈴木忠樹、前田 健.
    • Organizer
      第69回日本ウイルス学会 (長崎)
    • Related Report
      2022 Annual Research Report
  • [Presentation] 経鼻COVID-19組換えタンパク質ワクチンは広域中和能をもつIgA抗体を誘導できる.2022

    • Author(s)
      逸見拓矢、相内章、橋口隆生、石川青空、飛梅実、菅野隆行、岩田(吉河)奈織子、飯田俊、宮本翔、上野朗、佐野芳、田村浩二、鈴木亮介、長谷川秀樹、鈴木忠樹.
    • Organizer
      第26回日本ワクチン学会 (香川)
    • Related Report
      2022 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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