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

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

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 hea...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-57182-1
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Summary: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.
ISSN:2041-1723

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