Structural basis for hepatitis E virus neutralization by potent human antibodies
Year: 2025
Type: article
Abstract: 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.
Source: Science Advances
Institutions: Institut Pasteur, Université Paris Cité, École Nationale Vétérinaire d'Alfort, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, Centre National de la Recherche Scientifique, Inserm, Institut Toulousain des Maladies Infectieuses et Inflammatoires, Assistance Publique – Hôpitaux de Paris, Groupe Hospitalier Cochin - Port-Royal, Hôtel-Dieu, Broca - La Collégiale, Sorbonne Université, Centre de Recherche des Cordeliers
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,500
OpenAlex ID: W4410140315