Structural basis for hepatitis E virus neutralization by potent human antibodies
Antibodies targeting the hepatitis E virus (HEV) surface capsid protein (CA) are essential for infection control and resolution, yet their molecular and functional attributes remain largely elusive. We characterized 144 human HEV-CA-specific monoclonal antibodies cloned from the memory B cells of HEV-exposed individuals. Most human anti-CA antibodies cross-reacted with all HEV genotype variants, and a subset also recognized the zoonotic rat hepatitis E virus. HEV antibody repertoire was diverse and contained highly potent neutralizing antibodies binding to the CA protruding (P) domain. Structural analyses of CA protein complexed with three potent and broad HEV antibodies uncovered a neutralizing site located on monomeric P domain loops at the apex of the viral spike. These findings provide valuable insights into the protective humoral response to HEV and offer a framework for the rational design of HEV vaccines and immunotherapies.
Authors
- Vincent Olivier Mallet (ORCID: https://orcid.org/0000-0003-2219-9201)
- Hicham El Costa (ORCID: https://orcid.org/0000-0001-8889-9759)
- Eduard Baquero (ORCID: https://orcid.org/0000-0002-4701-4181)
- Cyril Planchais (ORCID: https://orcid.org/0000-0002-5142-7253)
- Cécile Alanio (ORCID: https://orcid.org/0000-0003-2785-7445)
- Virginie Doceul (ORCID: https://orcid.org/0000-0002-6286-3405)
- Hugo Mouquet (ORCID: https://orcid.org/0000-0002-4230-610X)
- Nicole Pavio (ORCID: https://orcid.org/0000-0001-6703-9418)
- Luis M. Molinos‐Albert (ORCID: https://orcid.org/0000-0001-5447-6803)
- Jordan D. Dimitrov (ORCID: https://orcid.org/0000-0001-8536-8995)
- Stanislas Pol (ORCID: https://orcid.org/0000-0001-9772-9591)
- Matthew L. Albert (ORCID: https://orcid.org/0000-0001-7285-6973)
- Estelle Mottez
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- École Nationale Vétérinaire d'Alfort (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Université Paris Cité (FR)
- Sorbonne Université (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Centre de Recherche des Cordeliers (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Maternité Port Royal (FR)
- Toulouse Mathematics Institute (FR)
- Groupe Hospitalier Cochin - Port-Royal, Hôtel-Dieu, Broca - La Collégiale (FR)
Publication Details
- Journal
- Science Advances
- Published
- 2025-05-07
- DOI
- https://doi.org/10.1126/sciadv.adu8811
- Citations
- 1
- Primary Topic
- Hepatitis Viruses Studies and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 1.32