Table 4. MERS-CoV candidate vaccines in development.
| Vaccine type | Examples | Vaccine design strategy | Comments | Refs |
|---|---|---|---|---|
| Live attenuated virus | rMERS-CoV-ΔE | Deletion of the gene encoding MERS-CoV E rendered the mutant virus replication-competent and propagation-defective |
• Attenuated SARS-CoV-ΔE mutant virus induced protection in mice and hamsters • No animal data are available for a rMERS-CoV-ΔE-based vaccine yet • Risk of disseminated infection in immunocompromised patients |
218,287,288,289,290,291,292,293,294,295 |
| DNA plasmid | MERS-CoV S DNA | DNA plasmids that encode full-length MERS-CoV S |
• BALB/cJ mice vaccinated with MERS-CoV S-encoding DNA developed neutralizing anti-MERS-CoV antibodies • The neutralizing antibody titre was boosted 10-fold after vaccination with S1 protein • Rhesus macaques vaccinated sequentially with MERS-CoV S-encoding DNA and S1 protein had reduced CT scan abnormalities |
219 |
| Viral vectors | MVA-MERS-S, Ad5-MERS-S, Ad5-MERS-S1, Ad5-S and Ad41-S | Viral vectors (MVA or Ad) that express full-length MERS-CoV S or the S1 subunit of MERS-CoV S |
• Both MVA and Ad vector-based vaccines induced neutralising anti-MERS-CoV antibodies in BALB/c mice • A MVA-MERS-S vaccine conferred mucosal immunity and induced serum neutralizing anti-MERS-CoV antibodies in dromedary camels • Mucosal (intragastric) administration of Ad5-S or Ad41-S vaccines induced the production of antigen-specific IgG and neutralizing antibodies, but not antigen-specific T cell responses, in BALB/c mice • Systemic (intramuscular) administration of Ad5-S or Ad41-S vaccines induced antigen-specific neutralizing IgG antibodies, as well as T cell responses in splenic and pulmonary lymphocytes • Increased immunopathology with severe hepatitis in SARS-CoV-infected ferrets that were previously vaccinated with an MVA-based vaccine expressing full-length SARS-CoV S |
220,221,222,223,224,298 |
| Nanoparticles | MERS-CoV S-containing nanoparticles | Purified MERS-CoV S-containing nanoparticles produced in insect (Sf9) cells that were infected with specific recombinant baculovirus containing the gene encoding MERS-CoV S |
• BALB/c mice vaccinated with MERS-CoV or SARS-CoV S-containing nanoparticles developed neutralizing antibodies specific to the viral S • Adjuvant matrix M1 or alum is required to elicit an optimal neutralizing antibody response |
225 |
| Virus-like particles | VRP-S | VEE virus-like replicon particles containing MERS-CoV S | Vaccination of BALB/c mice transduced with Ad5-hDPP4 with VRP-S reduced viral titres in lungs to nearly undetectable levels by day 1 after inoculation with MERS-CoV | 157 |
| Recombinant protein subunits | S(RBD)-Fc, S1(358–588)-Fc, S(377–588)-Fc and rRBD | Full-length MERS-CoV S or the RBD subunit of MERS-CoV S |
• Vaccinated BALB/c mice and/or rabbits developed neutralizing antibodies • Protective effects may be enhanced by combination with different adjuvants • Non-neutralizing epitopes in full-length S-based vaccines may induce antibody-mediated disease enhancement |
226,227,228,229,230,231,232,233 |
Ad, adenovirus; CoV, coronavirus; CT, computerized tomography; E, envelope protein; hDPP4, human dipeptidyl peptidase 4; IgG, immunoglobulin G; MERS, Middle East respiratory syndrome; MVA, modified vaccinia virus Ankara; RBD, receptor-binding domain; rRBD, recombinant RBD; S, spike glycoprotein; SARS,severe acute respiratory syndrome; S(RBD)-Fc, RBD of S fused to the antibody crystallizable fragment; S1(358–588)-Fc, amino acid residues 358–588 of the S1 subunit of S fused to the antibody crystallizable fragment; VEE, Venezuelan equine encephalitis; VRP, virus replicon particle.