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

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 Meyer, Sarah Prallet, Ann-Kathrin Mehnert, Anke R. M. Kraft, Lieven Verhoye, Carina Jacobsen, Eike Steinmann, Heiner Wedemeyer, Abel Viejo-Borbolla, Viet Loan Dao Thi, Thomas Pietschmann, Marc Lütgehetmann, Philip Meuleman, Maura Dandri, Thomas Krey (thomas.krey@uni-luebeck.de) and Patrick Behrendt (patrick.behrendt@twincore.de)
Additional contact information
George Ssebyatika: University of Luebeck
Katja Dinkelborg: A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical School
Luisa J. Ströh: Hannover Medical School
Florian Hinte: German Center for Infection Research (DZIF)
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
Lieven Verhoye: Ghent University
Carina Jacobsen: Hannover Medical School
Eike Steinmann: Ruhr University Bochum
Heiner Wedemeyer: Hannover Medical School
Abel Viejo-Borbolla: Hannover Medical School
Viet Loan Dao Thi: German Center for Infection Research (DZIF)
Thomas Pietschmann: A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical School
Marc Lütgehetmann: German Center for Infection Research (DZIF)
Philip Meuleman: Ghent University
Maura Dandri: German Center for Infection Research (DZIF)
Thomas Krey: University of Luebeck
Patrick Behrendt: A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical School

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-57182-1

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