Journal Article

PUBDB-2025-04168

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice

Ssebyatika, G. ; Dinkelborg, K. ; Ströh, L. J. ; Hinte, F. ; Corneillie, L. ; Hueffner, L. ; Guzman, E. M. ; Nankya, P. L. ; Plückebaum, N. ; Fehlau, L. ; Garn, J. ; Meyer, N. ; Prallet, S. ; Mehnert, A.-K. ; Kraft, A. R. M. ; Verhoye, L. ; Jacobsen, C. ; Steinmann, E. ; Wedemeyer, H. ; Viejo-Borbolla, A. ; Dao Thi, V. L. ; Pietschmann, T. ; Lütgehetmann, M. ; Meuleman, P. ; Dandri, M. ; Krey, T. (Corresponding author)Extern*EMBL* ; Behrendt, P. (Corresponding author)

2025
Springer Nature [London]

This record in other databases:      

Please use a persistent id in citations: doi:10.1038/s41467-025-57182-1  doi:10.3204/PUBDB-2025-04168

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.

---

Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
2. DFG project G:(GEPRIS)390874280 - EXC 2155: RESIST - Resolving Infection Susceptibility (390874280) (390874280)
3. SFB 900 B10 - Konformationelle Flexibilität der Hepatitis C Virus Glykoproteine als virale Evasionsstrategie gegen neutralisierende Antikörper (B10) (314569734) (314569734)

Experiment(s):

1. PETRA Beamline P11 (PETRA III)
2. PETRA Beamline P13 (PETRA III)

Appears in the scientific report 2025

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---