Subunit vaccines based on the full-length S protein cover both RBD and non-RBD neutralizing epitopes, some of which may be located in the conserved S2 subunit; thus this type of subunit vaccines are expected to induce high-titer neutralizing antibodies. Although several MERS-CoV full-length S protein-based vaccines have been reported in other vaccine types, including viral vectors and DNAs (Wang et al., 2015; Wang C. et al., 2017; Haagmans et al., 2016; Zhou et al., 2018), only a few subunit vaccines have been developed that rely on the full-length S protein. For example, a recombinant MERS-CoV S protein trimer (MERS S-2P) in prefusion conformation binds to the DPP4 receptor, as well as to the MERS-CoV NTD, RBD, and S2-specific neutralizing mAbs (Pallesen et al., 2017). Whereas this protein induces neutralizing antibodies in mice against divergent pseudotyped MERS-CoV in vitro, its in vivo protective activity against MERS-CoV infection is unknown (Pallesen et al., 2017). Therefore, more studies are needed to elucidate the potential for the development of MERS-CoV full-length S-based subunit vaccines, including understanding their protective efficacy and identifying possible harmful immune responses.