Co-crystallographic analyses of MERS-CoV RBD and/or RBD/DPP4 complexes have confirmed that the RBD is attributed to residues 367–588 (Chen et al., 2013) or 367–606 (Lu et al., 2013) in the MERS-CoV S1 subunit. Indeed, a recombinant MERS-CoV RBD (rRBD) fragment (residues 367–606) elicits RBD-specific antibody and cellular immune responses and neutralizing antibodies in mice and/or non-human primates (NHPs) (Lan et al., 2014, 2015). However, it only partially protects NHPs from MERS-CoV infection by alleviating pneumonia and clinical manifestations, as well as decreasing viral load (Lan et al., 2015). In addition, an RBD protein fragment containing MERS-CoV S residues 377–622 fused with the Fc tag of human IgG can induce MERS-CoV S1- and/or RBD-specific humoral and cellular immune responses in the immunized mice with neutralizing activity against MERS-CoV infection (Du et al., 2013c; Jiang et al., 2013). However, after comparing several versions of MERS-CoV RBD fragments with different lengths, it was found that a truncated RBD (residues 377–588) had the highest DPP4-binding affinity and induced the highest-titer IgG antibodies and neutralizing antibodies against MERS-CoV, identifying its role as a critical neutralizing domain (Ma et al., 2014b).