SARS subunit vaccines based on S protein fragments (S1 and S2), other than the RBD, have shown immunogenicity and/or protective efficacy against SARS-CoV infection (Guo et al., 2005; Li et al., 2013). For example, recombinant S1 proteins fused with or without foldon elicited specific antibodies with neutralizing activity that protected immunized mice against high-dose SARS-CoV challenge (Li et al., 2013). Although some studies have demonstrated that recombinant SARS-CoV S2 (residues 681–980) protein elicits specific non-neutralizing antibody response in mice (Guo et al., 2005), others have indicated that mAbs targeting highly conserved heptad repeat 1 (HR1) and HR2 domains of SARS-CoV S protein have broad neutralizing activity against pseudotyped SARS-CoV expressing S protein of divergent strains (Elshabrawy et al., 2012), indicating the potential of utilizing the S2 region as a broad-spectrum anti-SARS-CoV vaccine target (Zheng et al., 2009).