The S protein of SARS-CoV and MERS-CoV plays a vital role in receptor binding and membrane fusion. Thus, the S protein, but not other structural proteins, is the major antigen to induce protective neutralizing antibodies to block viruses from binding their respective receptor and thus inhibit viral infection (Bisht et al., 2004; Buchholz et al., 2004; Bukreyev et al., 2004; Yang et al., 2004). As a result, the S protein is also a major target for the development of subunit vaccines against SARS-CoV and MERS-CoV. Both full-length S protein and its antigenic fragments, including S1 subunit, NTD, RBD, and S2 subunit, can serve as important targets for the development of subunit vaccines (Guo et al., 2005; Mou et al., 2013; Wang et al., 2015; Jiaming et al., 2017; Zhou et al., 2018).