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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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
26 February 2025
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| In: |
Nature Communications
Year: 2025, Jahrgang: 16, Pages: 1-13 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-025-57182-1 |
| Online-Zugang: | 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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| Verfasserangaben: | 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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| 245 | 1 | 0 | |a Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice |c 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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| 520 | |a 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. | ||
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