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Elucidation of the mechanism of severe viral infections

Research Project

Project/Area Number 22KJ2159
Project/Area Number (Other) 22J13220 (2022)
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeMulti-year Fund (2023)
Single-year Grants (2022)
Section国内
Review Section Basic Section 49060:Virology-related
Research InstitutionOsaka University

Principal Investigator

LIU YAFEI  大阪大学, 医学系研究科, 特別研究員(DC2)

Project Period (FY) 2023-03-08 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2023: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2022: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsSARS-CoV-2 / Enhancing antibodies / ACE2 / SARS-CoV2 / enhancing antibody / NTD-antibody / RBD-antibody
Outline of Research at the Start

Specific antibodies for SARS-CoV2 enhance the binding of ACE2 to the Wild-type spike. The omicron variant has a large number of mutations. This study followed up on our previous findings by investigating whether Omicron spikes induce specific enhancing antibodies against Omicron variants.

Outline of Annual Research Achievements

I advanced the identification of enhancing antibodies in SARS-CoV-2 variants. First, I discovered that Wild-type enhancing antibodies can also enhance the infection of the Delta variant. I also analyzed the mechanism of the enhancing antibodies. This part of the work has been made public on Biorxiv. Subsequently, the project has been extended from the initial Delta variant to the recently emerged Omicron XBB1.5 variant, which analyzes the functional mechanism of the enhancing antibody, and will be supplemented with data from JN.1 based on peer-review. Currently, the experiment on this topic is almost completed, and we plan to submit a manuscript in the near future.

Last year, I unexpectedly found that some RBD antibodies could enhance Delta pseudovirus infection in 293T-ACE2 at low concentrations. Further studies revealed a specific enhancement only on human ACE2, but not on monkey ACE2 cells. Also, I found that the enhancing effect of RBD antibody on high expression ACE2 but not low expression ACE2, similar to other research. Through the study, the relationship between high expression of ACE2 and antibody-enhanced viral infection was found. My next plan is to analyze and clarify the enhancement mechanism of RBD antibody, and complete the manuscript writing and publication.

During the two-year funding period, I presented once at the JSI annual meeting, published a review article as the first author introducing enhancing antibodies and SARS-CoV-2 antibodies, and also published a preprint article. As a main contributor, I co-authored three articles that were formally published.

Report

(2 results)
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • Research Products

    (5 results)

All 2022

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (2 results)

  • [Journal Article] Neutralizing and enhancing antibodies against SARS-CoV-22022

    • Author(s)
      Liu Yafei、Arase Hisashi
    • Journal Title

      Inflammation and Regeneration

      Volume: 42 Issue: 1

    • DOI

      10.1186/s41232-022-00233-7

    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] The SARS-CoV-2 Lambda variant exhibits enhanced infectivity and immune resistance2022

    • Author(s)
      Kimura Izumi、Kosugi Yusuke、Wu Jiaqi、other 17 authors、Saito Akatsuki、Nakagawa So、Sato Kei
    • Journal Title

      Cell Reports

      Volume: 38 Issue: 2 Pages: 110218-110218

    • DOI

      10.1016/j.celrep.2021.110218

    • NAID

      120007183813

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SARS-CoV-2 S2?targeted vaccination elicits broadly neutralizing antibodies2022

    • Author(s)
      Ng Kevin W.、Faulkner Nikhil、Finsterbusch Katja、Wu Mary、Harvey Ruth、Hussain Saira、Greco Maria、Liu Yafei、Kjaer Svend、Swanton Charles、Gandhi Sonia、Beale Rupert、Gamblin Steve J.、Cherepanov Peter、McCauley John、Daniels Rodney、Howell Michael、Arase Hisashi、Wack Andreas、Bauer David L.V.、Kassiotis George
    • Journal Title

      Science Translational Medicine

      Volume: 14 Issue: 655

    • DOI

      10.1126/scitranslmed.abn3715

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies.2022

    • Author(s)
      Liu Yafei
    • Organizer
      第17回生命医科学研究所ネットワーク国際シンポジウム
    • Related Report
      2022 Annual Research Report
  • [Presentation] Acquisition of resistance to wild-type spike-immune sera by emerging SARS-CoV-2 variants.2022

    • Author(s)
      Liu Yafei
    • Organizer
      第51回日本免疫学会学術集会
    • Related Report
      2022 Annual Research Report

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Published: 2022-04-28   Modified: 2024-12-25  

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