Name  Antigenicity and functionality  Adjuvant  Route  Animal models  Antibody response  Cellular immune response  Protection  References
Subunit vaccines based on SARS-CoV full-length or trimeric S protein
FL-S and EC-S proteins  Bind to SARS-CoV S1, NTD, RBD, and S2-specific mAbs  MPL + TDM  S.C.  BALB/c mice  Elicit SARS-CoV S-specific Abs (IgG, > 1: 2 × 105), neutralizing (> 1:2.4 × 104) pseudotyped SARS-CoV (Tor2, GD03, and SZ3 strains)  N/A  N/A  He et al., 2006a
S andS-foldon proteins  N/A  TiterMax Gold; Alum Hydro+MPL  S.C. or I.M.  BALB/c mice  Elicit SARS-CoV S-specific Abs (IgG, > 1:104) in mice, neutralizing (∼2.4 × 102 for S; ∼1:7 × 102 for S-foldon) live SARS-CoV (Urbani strain)  N/A  Protect vaccinated mice from challenge of SARS-CoV (Urbani strain, 105 TCID50) with undetectable viral load in lungs  Li et al., 2013
triSpike protein  N/A  Alum hydro  I.P. or S.C.  BALB/c mice; Hamsters  Elicits SARS-CoV S-specific mucosal and serum Abs (IgA and IgG) in mice and hamsters, blocking S-ACE2 receptor binding and neutralizing live SARS-CoV (HKU-39849 strain); induces ADE  N/A  Protects vaccinated hamsters from challenge of SARS-CoV (Urbani strain, 103 TCID50) with undetectable or reduced viral load in lungs  Kam et al., 2007; Jaume et al., 2012
Subunit vaccines based on SARS-CoV RBD protein
RBD-Fc protein  N/A  Freund’s  I.D. or I.M.  BALB/c mice; Rabbits  Elicits SARS-CoV S/RBD-specific Abs (IgG) in mice and rabbits, neutralizing pseudotyped (rabbits: ≥ 7.3 × 104) and live (mice: 1:4 × 103; rabbits: > 1:1.5 × 104) SARS-CoV (BJ01 strain)  N/A  Protects majority (4/5) of vaccinated mice from challenge of SARS-CoV (BJ01 strain, 106 TCID50), with one mouse showing mild alveolar damage in lungs  He et al., 2004; Du et al., 2007
RBD193-CHO; RBD219-CHO proteins  Binds to SARS-CoV RBD-specific mAbs (neutralizing 24H8, 31H12, 35B5, 33G4, 19B2; non-neutralizing 17H9)  Freund’s  S.C.  BALB/c mice  Elicit SARS-CoV RBD-specific Abs, neutralizing pseudotyped (< 1:104 for RBD193-CHO; 1:5.8 × 104 for RBD219-CHO) and live (< 1:103 for RBD193-CHO; 1:103 for RBD219-CHO) SARS-CoV (GZ50 strain)  Induce SARS-CoV RBD-specific cellular immune responses (IFN-γ, IL-2, IL-4, IL-10) in mice  Protect all (for RBD219-CHO) or majority (3/5, for RBD219-CHO) of vaccinated mice from challenge of SARS-CoV (GZ50 strain, 100 TCID50 for RBD193-CHO; 5 × 105 TCID50 for RBD219-CHO) with undetectable viral RNA or no, to reduced, viral load in lungs  Du et al., 2009c, 2010
RBD-293T protein  Binds to SARS-CoV RBD-specific mAbs (neutralizing 24H8, 31H12, 35B5, 33G4, 19B2; non-neutralizing 17H9)  SAS  S.C.  BALB/c mice  Elicits SARS-CoV RBD-specific Abs (IgG), neutralizing pseudotyped (1:6.9 × 105) and live (1:1.6 × 103) SARS-CoV (GZ50 strain)  N/A  Protects all vaccinated mice from challenge of SARS-CoV (GZ50 strain, 100 TCID50) with undetectable viral RNA and viral load in lungs  Du et al., 2009b
S318-510 protein  N/A  Alum; Alum + CpG  S.C.  129S6/SvEv mice  Elicits SARS-CoV-specific Abs (IgG, IgG1, and IgG2a) in mice. Reduces neutralization after removing glycosylation  Induces SARS-CoV S-specific cellular immune responses (IFN-γ) in mice  N/A  Zakhartchouk et al., 2007
Subunit vaccines based on non-RBD SARS-CoV S protein fragments
S1 and S1-foldon proteins  N/A  TiterMax Gold; Alum Hydro + MPL  S.C. or I.M.  BALB/c mice  Elicit SARS-CoV S-specific Abs (IgG, > 1:104) in mice, neutralizing (1:1.7 × 102 for S1; 1:90 for S1-foldon) live SARS-CoV (Urbani strain)  N/A  Protect vaccinated mice from challenge of SARS-CoV (Urbani strain, 105 TCID50) with undetectable viral load in lungs  Li et al., 2013
S2 protein  N/A  Freund’s  S.C.  BALB/c mice  Elicits SARS-CoV S2-specific Abs (IgG, 1:1.6 × 103) in mice with no neutralizing activity  Induces SARS-CoV S2-specific cellular immune responses (IFN-γ and IL-4) in mice  N/A  Guo et al., 2005
Subunit vaccines based on SARS-CoV non-S structural proteins (i.e. N and M)
rN protein  N/A  Freund’s  I.P.  BALB/c mice  Elicits SARS-CoV N-specific Abs (IgG (1:1.8 × 103), IgG1, and IgG2a) in mice  Induces cellular immune responses with up-regulated IFN-γ and IL-10 cytokines in mice  N/A  Zheng et al., 2009
rN protein  N/A  Montanide + CpG; Freund’s  S.C.  BALB/c mice  Elicits SARS-CoV N-specific Abs (IgG) in mice  Induces SARS-CoV N-specific cellular immune responses (IFN- γ) in mice  N/A  Liu et al., 2006
M1-31 and M132-161 peptides  Bind to sera from SARS patients or immunized mice and rabbits  Freund’s  I.D.  BALB/c mice; NZW rabbits  Induce SARS-CoV M-specific Abs (IgG) in rabbits  N/A  N/A  He et al., 2005b