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Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice

Author

Listed:
  • George Ssebyatika

    (University of Luebeck)

  • Katja Dinkelborg

    (A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical School
    Hannover Medical School
    German Center for Infection Research (DZIF))

  • Luisa J. Ströh

    (Hannover Medical School)

  • Florian Hinte

    (German Center for Infection Research (DZIF)
    University Medical Center Hamburg-Eppendorf)

  • Laura Corneillie

    (Ghent University)

  • Lucas Hueffner

    (A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical School)

  • Elina M. Guzman

    (University of Luebeck)

  • Prossie L. Nankya

    (University of Luebeck)

  • Nina Plückebaum

    (Hannover Medical School)

  • Lukas Fehlau

    (A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical School)

  • Jonathan Garn

    (A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical School)

  • Nele Meyer

    (A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical School)

  • Sarah Prallet

    (Center for Integrative Infectious Diseases Research (CIID))

  • Ann-Kathrin Mehnert

    (Center for Integrative Infectious Diseases Research (CIID))

  • Anke R. M. Kraft

    (Hannover Medical School
    German Center for Infection Research (DZIF)
    a joint venture between Helmholtz-Centre for Infection Research and Hannover Medical School)

  • Lieven Verhoye

    (Ghent University)

  • Carina Jacobsen

    (Hannover Medical School)

  • Eike Steinmann

    (Ruhr University Bochum)

  • Heiner Wedemeyer

    (Hannover Medical School
    German Center for Infection Research (DZIF)
    Hannover Medical School)

  • Abel Viejo-Borbolla

    (Hannover Medical School
    Hannover Medical School)

  • Viet Loan Dao Thi

    (German Center for Infection Research (DZIF)
    Center for Integrative Infectious Diseases Research (CIID))

  • Thomas Pietschmann

    (A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical School
    German Center for Infection Research (DZIF)
    Hannover Medical School)

  • Marc Lütgehetmann

    (German Center for Infection Research (DZIF)
    Virology and Hygiene)

  • Philip Meuleman

    (Ghent University)

  • Maura Dandri

    (German Center for Infection Research (DZIF)
    University Medical Center Hamburg-Eppendorf)

  • Thomas Krey

    (University of Luebeck
    German Center for Infection Research (DZIF)
    Hannover Medical School
    Hannover Medical School)

  • Patrick Behrendt

    (A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical School
    Hannover Medical School
    German Center for Infection Research (DZIF))

Abstract

Hepatitis E virus (HEV) causes 3.3 million symptomatic cases and 44,000 deaths per year. Chronic infections can arise in immunocompromised individuals, and pregnant women may suffer from fulminant disease as a consequence of HEV infection. Despite these important implications for public health, no specific antiviral treatment has been approved to date. Here, we report combined functional, biochemical, and X-ray crystallographic studies that characterize the human antibody response in convalescent HEV patients. We identified a class of potent and broadly neutralizing human antibodies (bnAbs), targeting a quaternary epitope located at the tip of the HEV capsid protein pORF2 that contains an N-glycosylation motif and is conserved across members of the Hepeviridae. These glycan-sensitive bnAbs specifically recognize the non-glycosylated pORF2 present in infectious particles but not the secreted glycosylated form acting as antibody decoy. Our most potent bnAb protects human liver-chimeric mice from intraperitoneal HEV challenge and co-housing exposure. These results provide insights into the bnAb response to this important emerging pathogen and support the development of glycan-sensitive antibodies to combat HEV infection.

Suggested Citation

  • George Ssebyatika & Katja Dinkelborg & Luisa J. Ströh & Florian Hinte & Laura Corneillie & Lucas Hueffner & Elina M. Guzman & Prossie L. Nankya & Nina Plückebaum & Lukas Fehlau & Jonathan Garn & Nele , 2025. "Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57182-1
    DOI: 10.1038/s41467-025-57182-1
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    References listed on IDEAS

    as
    1. Gui-Ping Wen & Linling He & Zi-Min Tang & Si-Ling Wang & Xu Zhang & Yuan-Zhi Chen & Xiaohe Lin & Chang Liu & Jia-Xin Chen & Dong Ying & Zi-Hao Chen & Ying-Bin Wang & Wen-Xin Luo & Shou-Jie Huang & Sha, 2020. "Quantitative evaluation of protective antibody response induced by hepatitis E vaccine in humans," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    2. Viet Loan Dao Thi & Xianfang Wu & Rachel L. Belote & Ursula Andreo & Constantin N. Takacs & Joseph P. Fernandez & Luis Andre Vale-Silva & Sarah Prallet & Charlotte C. Decker & Rebecca M. Fu & Bingqian, 2020. "Stem cell-derived polarized hepatocytes," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    3. Delphine Planas & Nell Saunders & Piet Maes & Florence Guivel-Benhassine & Cyril Planchais & Julian Buchrieser & William-Henry Bolland & Françoise Porrot & Isabelle Staropoli & Frederic Lemoine & Hélè, 2022. "Considerable escape of SARS-CoV-2 Omicron to antibody neutralization," Nature, Nature, vol. 602(7898), pages 671-675, February.
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