Functional epitopes on hepatitis E virions and recombinant capsids are highly conformation-dependent

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Hepatitis E virus (HEV) causes significant acute hepatitis globally, particularly in developing nations.
• The recent development of a licensed vaccine has made Hepatitis E a preventable disease.
• Functional and neutralizing monoclonal antibodies (mAbs) often display high sensitivity to antigen conformation.

Purpose of the Study:

• To characterize the conformational sensitivity of antibodies in human and mouse serum samples against HEV.
• To compare the binding preferences of antibodies from naturally infected individuals, human vaccinees, and immunized mice.
• To validate the utility of enzyme-linked immunosorbent assays (ELISAs) for HEV serological assessment.

Main Methods:

• Comparative binding analysis using particulate and monomeric forms of the HEV truncated capsid protein.
• Functional assay to determine the inhibition of HEV subviral particle cell entry by antibodies.
• Determination of functional and binding titers in mouse serum samples.

Main Results:

• Antibodies in sera from naturally infected individuals, human vaccinees, and HEV p239-immunized mice showed a strong preference for particulate HEV antigens over monomeric forms.
• The conformational discrimination by serum antibodies was comparable to that of well-characterized murine mAbs.
• A strong correlation was observed between functional and binding titers for anti-HEV antibodies in mouse sera.

Conclusions:

• Antibodies generated by natural HEV infection or vaccination exhibit conformational preferences for particulate antigens.
• The study supports the continued use of ELISAs for HEV serological testing, provided the coating antigen presents conformational, native-like epitopes, such as HEV p239.