Table 1.
Vaccines based on MERS-CoV RBD. Live MERS-CoV strains used for neutralization and challenge experiments, as well as vaccine-induced neutralizing-antibody titers, are described in parentheses.
| Name | Functionality and Antigenicity | Immunogenicity in Induction of Antibody Response | Immunogenicity in Induction of Cellular Immune Response | Protective Immunity | Ref. |
|---|---|---|---|---|---|
| RBD-[SSG]-FR and RBD-FR nanoparticles | Bind to DPP4 receptor; antisera block RBD-hDPP4 binding | Induce MERS-CoV RBD-specific antibodies (IgG, IgG1, IgG2a, IgG2b, IgA) in mice | Elicit MERS-CoV RBD-specific T-cell responses (IFN-γ, TNF-α) in mouse splenocytes | N/A | [89] |
| sVLP (spherical virus-like particle) |
N/A | Induces MERS-CoV RBD-specific antibodies (IgG) in mice, neutralizing pseudotyped MERS-CoV (1:320) | Elicits MERS-CoV RBD-specific cellular immune response (IFN-γ, IL-2, IL-4) in mouse splenocytes | N/A | [90] |
| rRBD (recombinant RBD) | N/A | Induces MERS-CoV RBD-specific antibodies (IgG, IgG1, IgG2a) in mice or NHPs, neutralizing pseudotyped (1:800 to 1:1,600) and live (EMC2012: 1:269 to 1:363) MERS-CoV | Elicits MERS-CoV RBD-specific cellular immune response (TNF-α, IFN-γ, IL-2, IL-4, IL-6) in mouse splenocytes or monkey PBMCs | Partially protects NHPs from MERS-CoV (EMC2012: 6.5 × 107 TCID50) infection with alleviated pneumonia and decreased viral load | [88,91] |
| RBD (S377-588)-Fc |
Binds strongly to soluble and cell-associated hDPP4 or cDPP4 receptors and MERS-CoV RBD-specific neutralizing mAbs (Mersmab1, m336, m337, m338) | Induces MERS-CoV S1-specific antibodies (IgG, IgG1, IgG2a) in mice and rabbits, cross-neutralizing 17 pseudotyped (>1:104), 2 live (EMC2012, London1-2012: ≥1:103) MERS-CoV, and 5 mAb escape mutants (>1:104) | Elicits MERS-CoV S1-specific cellular immune responses (IFN-γ, IL-2) in mouse splenocytes | Protects Ad5/hDPP4-transduced BALB/c mice and hDPP4-Tg mice (67% survival rate) from challenge by MERS-CoV (EMC2012: 105 PFU for BALB/c; 103–104 TCID50 for Tg), without toxicity or immune enhancement | [92,95,96,97,98,99] |
| 2012-RBD 2013-RBD 2014-RBD 2015-RBD Camel-RBD |
Bind strongly to hDPP4 and cDPP4 receptors and MERS-CoV RBD-specific mAbs (Mersmab1, m336, m337, m338) with high affinity | Induce MERS-CoV S1-specific antibodies (IgG, IgG1, IgG2a) in mice, potently cross-neutralizing 17 pseudotyped (≥1:104), 2 live (EMC2012, London1-2012: >1:102) MERS-CoV, and 5 mAb escape mutants (≥1:104) | N/A | N/A | [100] |
| RBD-Fd | Binds strongly to soluble and cell-associated hDPP4 receptors and MERS-CoV RBD-specific mAbs (Mersmab1, m336, m337, m338) | Induces robust and long-term MERS-CoV S1-specific antibodies (IgG, IgG1, IgG2a) in mice, neutralizing at least 9 pseudotyped (>1:104) and live (EMC2012: >1:103) MERS-CoV | N/A | Protects hDPP4-Tg mice (83% survival rate) from lethal MERS-CoV (EMC2012: 104 TCID50) challenge | [94] |
| RBD (T579N) | Binds strongly to soluble and cell-associated hDPP4 receptors and MERS-CoV RBD-specific mAbs (hHS-1, m336, m337, m338) | Induces highly potent neutralizing antibodies in mice against live MERS-CoV (EMC2012: >1:3 × 103) | N/A | Significantly enhances efficacy in fully protecting hDPP4-Tg mice (100% survival rate) from lethal MERS-CoV (EMC2012: 104 TCID50) challenge | [93] |
Note: Ad5, adenovirus 5; DPP4, dipeptidyl peptidase 4; cDPP4, camel DPP4; hDPP4, human DPP4; hDPP4-Tg, hDPP4-transgenic; Fd, foldon; FR, ferritin; mAb, monoclonal antibody; N/A, not available or not applicable; NHP, non-human primate; PBMCs, peripheral blood mononuclear cells; PFU, plaque-forming unit; RBD, receptor-binding domain; S, spike; TCID50, median tissue-culture infectious dose.