Hepatitis E virus (HEV) is a lesser-known hepatitis virus, but its worldwide spread is doubtless and has increased recent years. Zoonotic spread of HEV, mainly due to genotype (gt) 3, has emerged in developed countries in the past decade. The current study has shown for the first time that domestic pigs in Bulgaria are widely infected with HEV. There is a need for a method for the cost-effective detection of the HEV infection and production of HEV immunogenic proteins that can be used as diagnostic antigens for the serological tests. Also, in this study we have compared the results from a commercial ELISA and an in-house ELISA test based on HEV open reading frame (ORF) 2 protein produced in planta, the sensitivity and the specify of the tests were evaluated. The development of a HEV diagnostic kit based on plant-derived ORF2 capsid protein is our goal and this will help to reduce the cost of such a kit and to enable diagnoses of HEV in developing countries.