Molinos-Albert Luis M, Baquero Eduard, Planchais Cyril, Doceul Virginie, El Costa Hicham, Mottez Estelle, Mallet Vincent, Pol Stanislas, Albert Matthew L, Pavio Nicole, Alanio Cécile, Dimitrov Jordan D, Mouquet Hugo
Humoral Immunology Unit, Institut Pasteur, Université Paris Cité, 75015 Paris, France.
NanoImaging Core Facility, Centre de Ressources et Recherches Technologiques (C2RT), Institut Pasteur, Université Paris Cité, 75015 Paris, France.
Sci Adv. 2025 May 9;11(19):eadu8811. doi: 10.1126/sciadv.adu8811. Epub 2025 May 7.
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.
靶向戊型肝炎病毒（HEV）表面衣壳蛋白（CA）的抗体对于感染的控制和消除至关重要，但其分子和功能特性在很大程度上仍不清楚。我们对从接触过HEV的个体的记忆B细胞中克隆出的144种人类HEV-CA特异性单克隆抗体进行了表征。大多数人类抗CA抗体与所有HEV基因型变体发生交叉反应，并且有一部分还识别出动物性大鼠戊型肝炎病毒。HEV抗体库具有多样性，包含与CA突出（P）结构域结合的高效中和抗体。对与三种强效且广谱的HEV抗体复合的CA蛋白进行的结构分析揭示了一个位于病毒刺突顶端的单体P结构域环上的中和位点。这些发现为针对HEV的保护性体液反应提供了有价值的见解，并为合理设计HEV疫苗和免疫疗法提供了框架。
