Lessons from hepatitis E vaccine design

•Hepatitis E vaccine derived from E. coli proved to be a successful B-cell vaccine.•Antigenicity and immunogenicity are prerequisite considerations in vaccine design.•The structural insights gained from studying B-cell epitopes of HEV are reviewed.•The scalable process and efficacy of the p239 vaccine using E. coli are described.•Our experience offers a paradigm for similar vaccine designs based on B-cell epitopes.

Acute hepatitis E is still a major public health issue, especially in developing countries, and hepatitis E virus (HEV) infection will likely only be preventable through prophylactic vaccines. In this review, we describe the lessons learnt from developing the first commercial hepatitis E vaccine (Hecolin), launched to market in China in 2012. The antigenicity and immunogenicity of VLP immunogens concomitant with the scalable Escherichia coli system and our large-scale clinical verification resulted in the success of our vaccine. The structures of the HEV capsid protein in complex with different antibodies provide important molecular insights into capsid assembly and antibody neutralization of the virus, providing a paradigm for B-cell epitope-based vaccine design.