The Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the group of highly pathogenic beta-coronaviruses that have been identified as priority pathogens by the WHO. Infection may lead to pneumonia and multi-organ failure, and is associated with a case fatality rate of up to 35%. Since its emergence in 2012, MERS-CoV has caused multiple outbreaks and has been exported to 27 countries. However, to date there is no licensed vaccine or specific therapy available. MVA-MERS-S is a novel modified vaccinia Ankara (MVA)-based vaccine candidate against the MERS-CoV encoding for the full spike glycoprotein (S). We report data from two investigator-initiated phase-1 clinical trials (IIT) investigating the safety and immunogenicity of MVA-MERS-S. The candidate vaccine was found to be safe and well-tolerated. Neutralizing and non-neutralizing antibody responses (ADNK, ADCP) and T cell immunity were detectable following MVA-MERS immunization. Vaccine dose and immunization intervals impacted the magnitude of antibody responses. Four immunodominant MERS-CoV-S-specific linear B-cell epitopes were identified using microarrays mapping the proteome of MERS-CoV-S.