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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-02-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57182-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850029702072238080 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | George Ssebyatika |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-70fc6f1c219946bf8d2d9052b8b8987c |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-70fc6f1c219946bf8d2d9052b8b8987c2025-08-20T02:59:28ZengNature PortfolioNature Communications2041-17232025-02-0116111310.1038/s41467-025-57182-1Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric miceGeorge Ssebyatika0Katja Dinkelborg1Luisa J. Ströh2Florian Hinte3Laura Corneillie4Lucas Hueffner5Elina M. Guzman6Prossie L. Nankya7Nina Plückebaum8Lukas Fehlau9Jonathan Garn10Nele Meyer11Sarah Prallet12Ann-Kathrin Mehnert13Anke R. M. Kraft14Lieven Verhoye15Carina Jacobsen16Eike Steinmann17Heiner Wedemeyer18Abel Viejo-Borbolla19Viet Loan Dao Thi20Thomas Pietschmann21Marc Lütgehetmann22Philip Meuleman23Maura Dandri24Thomas Krey25Patrick Behrendt26Center of Structural and Cell Biology in Medicine, Institute of Biochemistry, University of LuebeckTWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical SchoolInstitute of Virology, Hannover Medical SchoolGerman Center for Infection Research (DZIF)Laboratory of Liver Infectious Diseases, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent UniversityTWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical SchoolCenter of Structural and Cell Biology in Medicine, Institute of Biochemistry, University of LuebeckCenter of Structural and Cell Biology in Medicine, Institute of Biochemistry, University of LuebeckInstitute of Virology, Hannover Medical SchoolTWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical SchoolTWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical SchoolTWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical SchoolSchaller Research Group, Department of Infectious Diseases, Virology, University Hospital Heidelberg, Center for Integrative Infectious Diseases Research (CIID)Schaller Research Group, Department of Infectious Diseases, Virology, University Hospital Heidelberg, Center for Integrative Infectious Diseases Research (CIID)Department of Gastroenterology, Hepatology, Infectious diseases and Endocrinology, Hannover Medical SchoolLaboratory of Liver Infectious Diseases, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent UniversityInstitute of Virology, Hannover Medical SchoolDepartment of Molecular and Medical Virology, Ruhr University BochumDepartment of Gastroenterology, Hepatology, Infectious diseases and Endocrinology, Hannover Medical SchoolInstitute of Virology, Hannover Medical SchoolGerman Center for Infection Research (DZIF)TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical SchoolGerman Center for Infection Research (DZIF)Laboratory of Liver Infectious Diseases, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent UniversityGerman Center for Infection Research (DZIF)Center of Structural and Cell Biology in Medicine, Institute of Biochemistry, University of LuebeckTWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between Helmholtz-Centre for Infection Research and Hannover Medical SchoolAbstract 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.https://doi.org/10.1038/s41467-025-57182-1 |
| spellingShingle | 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 Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice Nature Communications |
| title | Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice |
| title_full | Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice |
| title_fullStr | Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice |
| title_full_unstemmed | Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice |
| title_short | Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice |
| title_sort | broadly neutralizing antibodies isolated from hev convalescents confer protective effects in human liver chimeric mice |
| url | https://doi.org/10.1038/s41467-025-57182-1 |
| work_keys_str_mv | AT georgessebyatika broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT katjadinkelborg broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT luisajstroh broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT florianhinte broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT lauracorneillie broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT lucashueffner broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT elinamguzman broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT prossielnankya broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT ninapluckebaum broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT lukasfehlau broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT jonathangarn broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT nelemeyer broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT sarahprallet broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT annkathrinmehnert broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT ankermkraft broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT lievenverhoye broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT carinajacobsen broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT eikesteinmann broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT heinerwedemeyer broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT abelviejoborbolla broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT vietloandaothi broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT thomaspietschmann broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT marclutgehetmann broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT philipmeuleman broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT mauradandri broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT thomaskrey broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice AT patrickbehrendt broadlyneutralizingantibodiesisolatedfromhevconvalescentsconferprotectiveeffectsinhumanliverchimericmice |