Table 2.
MERS-CoV protein-based vaccine candidates
| Vaccine platform | Vaccine candidate | Target antigen | Animal model | Route; adjuvant | Immunological response |
Efficacy | Reference | ||
|---|---|---|---|---|---|---|---|---|---|
| Nab | T-cell | ||||||||
| Virus-like particles | MERS-CoV VLPs | S,M,E | NHP | 4x i.m.;alum | + | + | ND | [60] | |
| Nanoparticle vaccine | S | S | mice | 2x i.m.;alum/Matrix M1 | + | ND | ND | [61] | |
| Recombinant proteins | S1 | S1 | S1 | mice | 2x i.m. | + | ND | ND | [58] |
| NHP | 2x i.m. | + | ND | protective | [58] | ||||
| RBD Subunit Vaccines | RBD-Fc | S358-588 | Rabbit | i.m.; incomplete Freund’s | + | ND | ND | [48] | |
| rRBD | S367-606 | NHP | 3x i.m.; alum | + | + | Protective | [64] | ||
| rRBD | S367–606 | mice | 3x i.m.;alum/CpG ODNa | ++ | + | ND | [65] | ||
| RBD-Fc | S377-588b | Ad/hDPP4-mice | 3x s.c. +MF59c | + | + | protective | [66, 67, 68] | ||
| Trimer RBD-Fc | S377-588 | Ad/hDPP4-mice | 2x i.m. + alum | + | ND | Protective | [69] | ||
| RBD-Fc | S377-662 | mice | 5x i.n.; Poly(I:C)d | + | + | ND | [70] | ||
| Extra-RBD targets | rNTD | S18-353 | Ad/hDPP4-mice | 3x i.m.;alum + CpG | + | + | Protective | [63] | |
| SP3 | S736–761-KLH | Rabbit | Prime: CFA; 3x boost: incomplete Freund’s | + | ND | [62] | |||
Ad/hDPP4-mice, mice transduced with hDPP4 in an adenoviral vector; alum, aluminum hydroxide; E, envelope protein; hDPP4, human dipeptidyl peptidase 4; i.m., intramuscular; i.n., intranasal; M, matrix protein; MERS-CoV, Middle East respiratory syndrome coronavirus; Nab, neutralizing antibodies; ND, not done; NHP, non-human primate; rNTD, recombinant N-terminal domain; RBD, receptor-binding domain; rRBD, recombinant RBD; RBD-Fc, RBD fused to the antibody crystallizable fragment of human IgG; S, spike protein; S1, S1 domain of spike protein; S367–606, amino acid residues 367–606 of the S protein; S736–761-KLH, peptide S736–761 coupled to keyhole limpet haemocyanin; s.c., subcutaneous; VLPs, Virus-like particles;
i.m.;alum/CpG ODN produced higher neutralizing antibody responses than s.c.; IFA/CpG ODN.
S350-588-Fc, S358-588-Fc, S367-588-Fc, S367-606-Fc, and S377-588-Fc were tested and S377-588-Fc had the highest Nab titers although some produced equal S1 IgG response [66].
MF59 produced the highest immunogenicity at low doses of antigen compared to S377-588-Fc only, or with Freund’s/Alum/mPLA-SM/ISA51/MF59. [67] 1 mg of antigen with MF59 was sufficient to produce humoral and cellular immune responses similar to higher doses (5 mg or 20 mg) [68].
i.n. + poly(I:C) vaccination induced stronger systemic cellular responses and higher local immune responses in mice lungs (IgA and neutralizing antibody titers) than s.c. + Montanide ISA51 vaccination.