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 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.
Authors
- Maura Dandri (ORCID: https://orcid.org/0000-0002-0073-6689)
- Laura Corneillie (ORCID: https://orcid.org/0000-0003-3937-7000)
- Patrick Behrendt (ORCID: https://orcid.org/0000-0001-5750-4259)
- Sarah Prallet
- Elina Muriel Guzmán (ORCID: https://orcid.org/0009-0002-6956-3402)
- Abel Viejo‐Borbolla (ORCID: https://orcid.org/0000-0001-6395-4010)
- Thomas Krey (ORCID: https://orcid.org/0000-0002-4548-7241)
- Nuala J. Meyer (ORCID: https://orcid.org/0000-0003-4597-5584)
- Nina Plückebaum (ORCID: https://orcid.org/0000-0002-9788-7335)
- George Ssebyatika (ORCID: https://orcid.org/0000-0001-5350-3371)
- Florian Hinte
- Jonathan Garn
- Philip Meuleman (ORCID: https://orcid.org/0000-0001-6821-234X)
- Ann-Kathrin Mehnert
- Eike Steinmann (ORCID: https://orcid.org/0000-0002-3654-9965)
- Lucas Hueffner
- Heiner H. Wedemeyer (ORCID: https://orcid.org/0000-0003-2906-0480)
- Viet Loan Dao Thi (ORCID: https://orcid.org/0000-0003-2293-3592)
- Prossie Lindah Nankya
- Lukas Fehlau
- Carina Jacobsen (ORCID: https://orcid.org/0000-0002-1418-1514)
- Anke Kraft (ORCID: https://orcid.org/0000-0002-9666-0753)
- Katja Dinkelborg (ORCID: https://orcid.org/0009-0006-0858-6124)
- Lieven Verhoye (ORCID: https://orcid.org/0000-0001-8216-5578)
- L.J. Stroh (ORCID: https://orcid.org/0000-0002-2781-2303)
- Thomas Pietschmann (ORCID: https://orcid.org/0000-0001-6789-4422)
- Marc Lütgehetmann (ORCID: https://orcid.org/0000-0002-9468-7944)
Institutions
- Universität Hamburg (DE)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Ghent University (BE)
- Medizinische Hochschule Hannover (DE)
- Institute for Integrative and Experimental Genomics (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- German Center for Infection Research (DE)
- Helmholtz Centre for Infection Research (DE)
- Centre for Individualised Infection Medicine (DE)
- Center for Experimental and Clinical Infection Research (DE)
- Centre for Structural Systems Biology (DE)
- Ruhr University Bochum (DE)
- University of Lübeck (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-02-26
- DOI
- https://doi.org/10.1038/s41467-025-57182-1
- Citations
- 9
- Primary Topic
- Hepatitis Viruses Studies and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 11.90
Funders
- Deutsches Zentrum für Infektionsforschung
- Deutsche Forschungsgemeinschaft
- Volkswagen Foundation
- Fonds Wetenschappelijk Onderzoek