Plotkin's Vaccines (Eighth Edition): Chapter 29 - Hepatitis E Vaccines

For many years, hepatitis E was thought to be largely restricted to endemic developing countries where hepatitis E virus (HEV) genotypes 1 and 2 are transmitted by contaminated water and cause large epidemics in association with monsoon rains in Asia or during humanitarian crises in Africa. It is now estrablished that hepatitis E is endemic in many developed countries where it is a porcine zoonosis caused by HEV genotypes 3 and 4. HEV is responsible of life-theatening illness in vulnerable populations including pregnant women in developing countries. Chronic hepatitis associated to HEV genotypes 3 and 4 can also develop in persons who are immunocompromised. Soon after the molecular cloning of HEV in 1991, recombinant viral capsid antigens were expressed and tested in nonhuman primates for protection against infection and liver disease. Three virus-like particle vaccines against HEV based on the capsid protein (rHEV 56 kDa, HEV 239 and HEV p179) have been developed and entered clinical trials. Safety, immunogenicity, and efficacy in preclinical and clinical trials are described in this review. Although HEV 239 vaccine was licenced for use in China in 2011, several steps including prequalification by the World Health Organization are needed to make the vaccine available where it is most needed, in particular for use in large outbreaks in developing countries.