Hepatitis E is a type of liver disease caused by infection with the hepatitis E virus (HEV). In general, HEV causes an asymptomatic infection that spontaneously resolves. However, in some cases, symptoms of varying degree do occur, sometimes leading to fulminant hepatitis and death. Under special circumstances, the infected individual may even not be able to clear the infection and will become chronically infected. HEV circulates especially in low-income countries, but during the last decade, the number of diagnosed hepatitis E cases in Europe has tripled. Treatment is essentially limited to ribavirin, which is flawed by lack of specificity, emergence of resistance, induction of anemia and the fact that it cannot be used in all patient populations (e.g. pregnant women). In this project, we propose the development and pre-clinical in vivo characterization of a novel vaccine for the prevention of HEV infection. Since the design of our vaccine is based on the use of virus-like particles that are composed of a combination of wild type hepatitis B virus (HBV) surface protein with genetically engineered chimeric HEV/HBV proteins, it will simultaneously induce immunity to HEV and HBV. In addition, we will generate HEV-specific human monoclonal antibodies that could be used as post-exposure prophylaxis or immunotherapy. Using different cell culture and animal models we will study the immunogenicity of our vaccine and the efficacy of our two antiviral approaches.