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

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 s...

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Main Authors: Ssebyatika, George (Author) , Dinkelborg, Katja (Author) , Ströh, Luisa J. (Author) , Hinte, Florian (Author) , Corneillie, Laura (Author) , Hueffner, Lucas (Author) , Guzman, Elina M. (Author) , Nankya, Prossie L. (Author) , Plückebaum, Nina (Author) , Fehlau, Lukas (Author) , Garn, Jonathan (Author) , Meyer, Nele (Author) , Prallet, Sarah (Author) , Mehnert, Ann-Kathrin (Author) , Kraft, Anke R. M. (Author) , Verhoye, Lieven (Author) , Jacobsen, Carina (Author) , Steinmann, Eike (Author) , Wedemeyer, Heiner (Author) , Viejo-Borbolla, Abel (Author) , Dao Thi, Viet Loan (Author) , Pietschmann, Thomas (Author) , Lütgehetmann, Marc (Author) , Meuleman, Philip (Author) , Dandri, Maura (Author) , Krey, Thomas (Author) , Behrendt, Patrick (Author)
Format: Article (Journal)
Language:English
Published: 26 February 2025
In: Nature Communications
Year: 2025, Volume: 16, Pages: 1-13
ISSN:2041-1723
DOI:10.1038/s41467-025-57182-1
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-025-57182-1
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-025-57182-1
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Author Notes: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 & Patrick Behrendt
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Summary: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.
Item Description:Gesehen am 31.07.2025
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-025-57182-1

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