Structural basis for hepatitis E virus neutralization by potent human antibodies

Area of Science:

• Virology
• Immunology
• Structural Biology

Background:

• Antibodies targeting the hepatitis E virus (HEV) surface capsid protein (CA) are crucial for controlling and resolving HEV infection.
• However, the precise molecular and functional characteristics of these antibodies are not well understood.

Purpose of the Study:

• To characterize human HEV-CA-specific monoclonal antibodies (mAbs).
• To investigate the neutralizing capabilities and structural basis of HEV antibody responses.
• To identify potential targets for HEV vaccine and immunotherapy development.

Main Methods:

• Cloning and characterization of 144 human HEV-CA-specific mAbs from HEV-exposed individuals.
• Cross-reactivity analysis against various HEV genotypes and rat hepatitis E virus.
• Structural analysis of HEV-CA protein complexed with neutralizing antibodies.

Main Results:

• Most human anti-HEV CA antibodies exhibited broad cross-reactivity with different HEV genotypes and some recognized rat HEV.
• A diverse HEV antibody repertoire was identified, including highly potent neutralizing antibodies.
• Neutralizing antibodies were found to bind the protruding (P) domain of the HEV capsid protein.
• Structural studies revealed a key neutralizing site on the P domain loops at the viral spike apex.

Conclusions:

• The study elucidates the molecular and functional attributes of protective humoral responses against HEV.
• Identified neutralizing epitopes provide a basis for the rational design of novel HEV vaccines and immunotherapies.
• Characterized antibodies offer potential for developing effective immunotherapeutic strategies against HEV infections.