Name  Functionality and antigenicity  Adjuvant  Route  Animal models  Antibody response  Cellular immune response  Protective efficacy  References
Subunit vaccines based on MERS-CoV full-length S protein
MERS S-2P protein  Binds to DPP4 receptor and MERS-CoV S-NTD, RBD, and S2-specific neutralizing mAbs (G2, D12, and G4, respectively)  SAS  I.M.  BALB/c mice  Elicits neutralizing Abs in mice, neutralizing 7 pseudotyped MERS-CoV  N/A  N/A  Pallesen et al., 2017
Subunit vaccines based on MERS-CoV RBD protein
rRBD (S367-606) protein  N/A  Alum Hydro + CpG or poly(I:C); IFA + CpG (mouse); Alum (NHPs)  I.M. or S.C.  BALB/c mice; NHPs  Elicits MERS-CoV RBD-specific Abs in mice (IgG, IgG1, IgG2a, and IgG2b) and NHPs (IgG), neutralizing pseudotyped (mouse: < 1:5 × 102) and live (NHPs: < 1:5 × 102) MERS-CoV (EMC2012 strain)  Induces MERS-CoV RBD-specific cellular immune responses (IFN-γ, TNF-α, IL-2, IL-4, IL-6, and IL-10) in mice and/or monkeys  Partially protects vaccinated NHPs from challenge of MERS-CoV (EMC2012 strain, 6.5 × 107 TCID50) with alleviated pneumonia and decreased viral load  Lan et al., 2014, 2015
RBD (S377-662)-Fc protein  Binds to DPP4 receptor  Poly(I:C); Montanide  I.N. or S.C.  BALB/c mice  Elicits MERS-CoV S1- and RBD-specific Abs (IgA, IgG (> 1:104), IgG1, IgG2a, and IgG3) in mice, neutralizing (≥ 1:2.4 × 102) live MERS-CoV (EMC2012 strain)  Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice  N/A  Du et al., 2013c; Ma et al., 2014b
RBD (S377-588)-Fc protein  Binds to DPP4 receptor and MERS-CoV RBD specific neutralizing mAbs (Mersmab1, m336, m337, and m338)  Montanide; MF59; AddaVax  I.M. or S.C.  BALB/c mice; hDPP4-Tg mice; Rabbits  Elicits MERS-CoV S1 and RBD-specific Abs in mice (IgG (> 1:105), IgG1, and IgG2a) and rabbits (IgG), neutralizing 17 pseudotyped (≥ 1:104) and 2 live (≥ 1:103) MERS-CoV (EMC2012 and London1-2012 strains)  Induces MERS-CoV S1-specific cellular immune responses (IFN-γ and IL-2) in mice  Protects vaccinated Ad5/hDPP4-transduced BALB/c mice and majority (4/6) of vaccinated hDPP4-Tg mice from MERS-CoV (EMC2012 strain, 105 PFU for BALB/c; 103–4 TCID50 for Tg) challenge, without immunological toxicity or eosinophilic immune enhancement  Du et al., 2013a; Ma et al., 2014b; Tang et al., 2015; Zhang et al., 2016; Nyon et al., 2018
RBD-Fd protein  Binds to DPP4 receptor and MERS-CoV RBD-specific neutralizing mAbs (Mersmab1, m336, m337, and m338)  MF59; Alum  I.M. or S.C.  BALB/c mice; hDPP4-Tg mice  Elicits MERS-CoV S1-specific Abs (IgG (> 1:105), IgG1, and IgG2a) in mice, neutralizing at least 9 pseudotyped (> 1:104) and live (> 1:103) MERS-CoV (EMC2012 strain)  N/A  Protects majority (5/6) of vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50)  Tai et al., 2016
RBD (T579N) protein  Binds to receptor DPP4 and MERS-CoV RBD-specific neutralizing mAbs (hMS-1, m336, m337, and m338)  Montanide; Alum  I.M. or S.C.  BALB/c mice; hDPP4-Tg mice  Elicits neutralizing Abs (> 1:3 × 103) in mice against live MERS-CoV (EMC2012 strain)  N/A  Protects all vaccinated hDPP4-Tg mice from challenge of MERS-CoV (EMC2012 strain, 104 TCID50)  Du et al., 2016a
Subunit vaccines based on non-RBD MERS-CoV S protein fragments
S1 protein  N/A  Ribi; Alum pho  I.M.  BALB/c mice; NHPs  Elicits MERS-CoV S1-specific Abs in mice (IgG and IgG1) and NHPs (IgG), neutralizing 8 pseudotyped and live MERS-CoV (JordanN3 strain)  N/A  Protects vaccinated NHPs from challenge of MERS-CoV (JordanN3 strain, 5 × 106 PFU) with reduced abnormalities on chest CT  Wang et al., 2015
S1 protein  N/A  Advax + SAS  I.M.  Dromedary camels; Alpacas  Elicits neutralizing Abs in dromedary camels (≥ 1:80) and alpacas (≥ 1:6.4 × 102) against live MERS-CoV (EMC2012 strain)  N/A  Protects vaccinated dromedary camels and alpacas from challenge of MERS-CoV (EMC2012 strain, 107 TCID50) with reduced and delayed viral shedding in the upper airways (in camels) or complete protection (in alpacas)  Adney et al., 2019
rNTD protein  N/A  Alum pho + CpG  I.M.  BALB/c mice; Ad5-hDPP4 mice  Elicits MERS-CoV S-NTD-specific Abs (IgG, ≥ 1:104) in mice, neutralizing pseudotyped and live (1:40) MERS-CoV (EMC2012 strain)  Induces MERS-CoV S-NTD-specific cellular immune responses (IFN-γ, IL-2, IL-6, IL-10, and IL-17A) in mice  Protects vaccinated Ad5-hDPP4-transduced mice from challenge of MERS-CoV (EMC2012 strain, 105 PFU) with reduced lung abnormalities and respiratory tract pathology  Jiaming et al., 2017
SP3 peptide (aa736-761)  N/A  Freund’s  N/A  BALB/c mice; NZW rabbits  Elicits MERS-CoV S-specific Abs (IgG, 1:104) in rabbits, neutralizing pseudotyped MERS-CoV  N/A  N/A  Yang et al., 2014a