SARS-CoV Subunit Vaccines Based on Non-S Structural Proteins Subunit vaccines based on the N and M proteins of SARS-CoV have shown immunogenicity in vaccinated animals (Liu et al., 2006; Zheng et al., 2009). Studies have revealed that a plant-expressed SARS-CoV N protein conjugated with Freund’s adjuvant elicited specific IgG antibodies, including IgG1 and IgG2a subtypes, and cellular immune responses in mice, whereas another E. coli-expressed N protein conjugated with Montanide ISA-51 and cysteine-phosphate-guanine (CpG) adjuvants induced specific IgG antibodies toward a Th1 (IgG2a)-type response in mice (Liu et al., 2006; Zheng et al., 2009). Although N-specific antibodies have been detected in convalescent-phase SARS patient and immunized rabbit sera, they have no neutralizing activity against SARS-CoV infection (Qiu et al., 2005). In addition, immunodominant M protein peptides (M1-31 and M132-161) identified using convalescent-phase sera of SARS patients and immunized mouse and rabbit sera have immunogenicity to elicit specific IgG antibodies in rabbits (He et al., 2005b). In spite of their immunogenicity, it appears that these N- and M-based SARS subunit vaccines have not been investigated for their protective efficacy against SARS-CoV infection. Thus, it is unclear whether these non-S structural protein-based SARS subunit vaccines can prevent SARS-CoV infection.