Development of effective vaccines is urgently needed to control the spread of emerging MERS-CoV infections. While viral vector-based and live-attenuated virus-based vaccines have potential for providing effective immunity, subunit vaccines will offer the safestmeans for prevention. Although subunit-based vaccines might induce less immunogenicity than the other vaccine types, their effi-cacy can be significantly improved by rational design based on the structural analysis of RBD of MERS-CoV S protein and by identification of the most stable and critical neutralizing fragment of RBD,while eliminating non-neutralizing epitopes through immunofocusing