TABLE 2.
Potential vaccine candidates against Middle East respiratory syndrome-coronavirus.
| Vaccine type | Vector and antigen | Administration route | Results | References |
| Viral-vector | rAd5 encoding S1 protein | IM | Immunization with rAd5 constructs expressing CD40-targeted S1 fusion protein (rAd5-S1/F/CD40L) offered complete protection to hDPP4 transgenic mice against MERS-CoV challenge and prevented pulmonary perivascular hemorrhage. | Hashem et al., 2019 |
| rAd5 or rAd41 encoding S protein | IM or IG | IG administration of rAd5-S or rAd41-S elicited antigen-specific IgG and neutralizing antibody in serum, but T-cell responses were not detected. A single IM injection of Ad5-S or Ad41-S induced systemic humoral response in addition to the functional antigen-specific T-cell responses in the spleen and pulmonary lymphocytes of the mice, which persisted for several months. | Guo et al., 2015 | |
| rAd5 encoding S protein or S1 | IM and later boosted with IN | Immunized mice demonstrated antibody responses against spike protein, which neutralized MERS-CoV in vitro. Stronger neutralizing antibody responses were observed in the mice vaccinated with the vector encoding the shorter S1 protein than the full-length S protein. | Kim et al., 2014 | |
| ChAdOx1 encoding S protein* | IM or IN | Single dose intranasal or intramuscular immunization protected transgenic BALB/c mice against lethal virus challenge. Immunogenicity and efficacy were comparable between immunization routes. | Munster et al., 2017 | |
| ChAdOx1 encoding S protein* | IM | Single dose immunization with ChAdOx1 MERS vaccine with tPA induced 5 logs of neutralizing antibodies in BALB/c mice. | Alharbi et al., 2017 | |
| MVA encoding S protein | IM | Immunization with MVA MERS vaccine containing tPA regulated by F11 promoter induced 4.7 logs of neutralizing antibodies in BALB/c mice. | Alharbi et al., 2017 | |
| MVA encoding S protein∗∗ | IM or SC | Both immunization routes induced neutralizing antibodies and CD8+ T-cell responses in mice. Vaccinated mice were protected against MERS-CoV challenge infection after transduction with the hDPP4 receptor. | Volz et al., 2015 | |
| MVA encoding S protein∗∗ | IM | Neutralizing antibody responses were induced in immunized mice. | Song et al., 2013 | |
| MVA encoding the N-protein | IM or IP | CD8+ T-cell response was elicited in the immunized mice in both immunization routes. | Veit et al., 2018 | |
| NDV encoding S protein | IM | Recombinant NDV expressing MERS-CoV S protein induced neutralizing antibodies in BALB/c mice and Bactrian camels. | Liu et al., 2017 | |
| Viral-vector and nanoparticle | rAd5 and MERS-CoV S nanoparticle | IM | Heterologous prime-boost vaccination with rAd5-S protein and alum-adjuvanted recombinant S protein induced both Th1 and Th2 immune responses in SPF BALB/c mice. | Jung et al., 2018 |
| DNA | DNA encoding S protein∗∗∗ | IM followed by EP | The DNA vaccine was immunogenic in mice, camels and rhesus macaques. When the immunized macaques were challenged with MERS-CoV, characteristic clinical symptoms including pneumonia were reduced. | Muthumani et al., 2015 |
| DNA encoding S or S1 protein | IM | DNA encoding S1 protein elicited stronger antibody and cellular immune responses in mice than that encoding the S protein. Both DNAs encoding S1 and S proteins induced neutralizing antibodies that cross-reacted with MERS-CoV strains of human and camel origins. | Al-Amri et al., 2017 | |
| DNA encoding S1 protein | IM | Immunization with DNA encoding S1 protein and passive transfer of immune sera from the vaccinated mice protected hDPP4-transduced-mice from MERS-CoV infection. | Chi et al., 2017 | |
| Subunit | MERS-CoV S1 protein | SC | Adjuvanted (MF59) MERS-CoV S1 protein protected hDPP4 transgenic mice against lethal MERS-CoV challenge, where the protection correlated well with the neutralizing antibody titer. | Wang et al., 2017c |
| MERS-CoV S1 protein | IM | Immunization with adjuvanated (Advax HCXL adjuvant and Sigma Adjuvant System) S1 protein reduced and delayed virus shedding in the upper respiratory tract of dromedary camels and provided complete protection in alpaca against MERS-CoV challenge. | Adney et al., 2019 | |
| MERS-CoV S protein trimer on Fd | IM | Recombinant prefusion trimeric MERS-CoV S protein induced high titer of neutralizing antibodies in BALB/cJ mice. | Pallesen et al., 2017 | |
| RBD trimer on Fd | SC or IM | Adjuvanted (alum) RBD-Fd induced neutralizing antibodies in BALB/c mice and protected (83%) hDPP4 transgenic mice against lethal MERS-CoV challenge. | Tai et al., 2016 | |
| RBD fused to Fc | SC | Adjuvanted RBD-Fc induced high titer of neutralizing antibodies in BALB/c mice and New Zealand white rabbits. | Ma et al., 2014b | |
| RBD fused to Fc | SC | Mice immunized with the vaccine and Montanide ISA 51 adjuvant produced neutralizing antibodies which inhibited binding of the RBD to DPP4 receptor, neutralizing MERS-CoV infection. | Du et al., 2013 | |
| RBD fused to Fc | IN or SC | Mice vaccinated with both immunization routes in the presence of adjuvants (Montanide ISA 51 adjuvant for SC and Poly(I:C) for IN) elicited systemic humoral immune responses. Stronger systemic cellular immune responses and local mucosal immune responses were observed in mice immunized via IN route. | Ma et al., 2014a | |
| RBD fused to Fc | IM | hCD26/DPP4 transgenic mice immunized with the vaccine in the presence of adjuvant, AddaVax elicited neutralizing antibodies and were protected against MERS-CoV infection. | Nyon et al., 2018 | |
| RBD fused to Fc | SC | Mice immunized with the vaccine alone produced detectable neutralizing antibodies and cellular immune responses. Immunogenicity of the vaccine improved when the adjuvants such as Freund’s adjuvant, alum, monophosphoryl lipid A, Montanide ISA51 or MF59 was included in the formulation. MF59 was demonstrated to be superior in enhancing the vaccine immunogenicity and protection against viral challenge. | Zhang et al., 2016 | |
| Recombinant RBD | IM or SC | When the subunit vaccine was administered together with combination of alum and CpG ODN, optimized RBD-specific humoral and cellular immunity were elicted. Robust RBD-specific antibody and T-cell responses were induced in mice immunized with the vaccine in combination with IFA and CpG ODN, but low level of neutralizing antibodies were induced. | Lan et al., 2014 | |
| Recombinant RBD | IM | Rhesus macaques immunized with the subunit vaccine and alum adjuvant produced neutralizing antibodies and experienced mitigated clinical symptoms when challenged with MERS-CoV. | Lan et al., 2015 | |
| rNTD of S protein | IM | Immunization with rNTD of MERS-CoV S protein adjuvanted with alum induced neutralizing antibodies and reduced the respiratory tract pathology of BALB/c mice challenged with MERS-CoV. | Jiaming et al., 2017 | |
| VLPs | MERS-CoV VLPs | IM | Co-administration of the VLPs-based vaccine and alum activated RBD specific humoral and cellular immune responses in rhesus macaques. | Wang et al., 2017b |
| S protein nanoparticles | IM | S protein produced in the baculovirus insect cells expression system assembled into nanoparticles of approximately 25 nm. Mice immunized with these nanoparticles in the presence of alum produced high titer of neutralizing antibody. | Coleman et al., 2014 | |
| S protein nanoparticles | IM | The vaccine together with Matrix M1 adjuvant activated S protein specific humoral immune responses, and protected hDPP4 transduced mice against viral challenge. | Coleman et al., 2017 | |
| CPV VLP displaying RBD | IM | Immunization of the mice with the chimeric VLPs displaying RBD in the presence of adjuvants [alum or Poly(I:C)] elicited neutralizing antibody responses as well as cellular immune responses. | Wang et al., 2017a | |
| Influenza A VLP displaying S protein | IM | Immunization of the mice with the chimeric VLPs displaying RBD in the presence of a combination of adjuvants (alum and CpG ODN) elicited neutralizing antibody responses. | Lan et al., 2018 | |
| Nanoparticle | Ferritin displaying RBD | IM | Immunization with chaperna-mediated ferritin nanoparticle displaying MERS-CoV RBD adjuvanted with MF59 induced RBD-specific antibodies in BALB/c mice which inhibited RBD binding to hDPP4 receptor protein. | Kim et al., 2018 |
| Inactivated whole -virus | MERS-CoV | IM | Mice immunized with the inactivated vaccine in the presence of a combination of adjuvants (alum and CpG ODN) elicited neutralizing activity but not cell-mediated immunity. This vaccine also protected hDPP4 transduced mice against MERS-CoV challenge. | Deng et al., 2018 |
| MERS-CoV | IM | Gamma radiation-inactivated MERS-CoV induced neutralizing antibodies and reduced viral load in hDPP4 transgenic mice but may cause hypersensitivity-type lung immunopathologic reaction upon MERS-CoV challenge. | Agrawal et al., 2016 | |
| Chimeric RABV displaying S1 protein | IM | The inactivated vaccine induced high titer of neutralizing antibodies in mice, and protected hDPP4-transduced-mice against MERS-CoV infection. | Wirblich et al., 2017 | |
| Live-attenuated | MERS-CoV mutant | - | The mutant was produced by deleting the E gene of the MERS-CoV. This mutant lacked infectivity but was single-cycle replicative. | Almazan et al., 2013 |
| MERS-CoV mutant | IN | Attenuated MERS-CoV through mutation of NSP16 (D130A) protected CRISPR-Cas9- targeted 288–330+/+ C57BL/6 mice from mouse-adapted MERS-CoV challenge. | Menachery et al., 2017 | |
| MV expressing full-length or truncated, soluble variant of S protein | IP | The recombinant MV was replication competent. Immunization of the type I interferon receptor-deficient (IFNAR–/–) CD46Ge mice with the recombinant MV induced both MV and S protein specific neutralizing antibodies as well as cellular immune responses. The recombinant MV protected hDPP4-transduced-mice against viral challenge. | Malczyk et al., 2015 | |
| MV expressing N protein | IP | Recombinant MV expressing MERS-CoV N protein induced N-specific T cell responses in IFNAR–/–-CD46Ge mice. | Bodmer et al., 2018 | |
| Recombinant VSV expressing S protein | IN or IM | Recombinant VSV was produced by replacing the glycoprotein of VSV with the S protein of MERS-CoV. The recombinant virus induced neutralizing antibodies and T cell responses in rhesus macaques after a single intramuscular or intranasal immunization dose. | Liu et al., 2018 |
MERS-CoV, Middle East respiratory syndrome-coronavirus; rAd5, recombinant human adenovirus type-5; rAd41, recombinant human adenovirus type-41; MVA, modified vaccinia virus Ankara; ChAdOx1, chimpanzee adenovirus, Oxford University #1; NDV, Newcastle disease virus; MV, measles virus; CPV, canine parvovirus; RABV, rabies virus; VLP, virus-like particle; NSP, non-structural protein; S protein, spike protein; S1 protein, spike protein receptor binding subunit; RBD, receptor-binding domain in S1; N protein, nucleocapsid protein; rNTD, recombinant N-terminal domain; Fd, foldon trimerization motif; Fc, Fc region of human IgG; tPA, leader sequence of the human tissue plasminogen activator gene; IFNAR–/–-CD46Ge mice, genetically modified mice deficient of type I IFN receptor and transgenically expressing human CD46; SPF, specific-pathogen-free; IM, intramuscular; IN, intranasal; IP, intraperitoneal; SC, subcutaneous; IG, intragastric; EP, electroporation. Vectors and antigens marked with “*” have entered phase I clinical trial (*MERS001; ∗∗MVA-MERS-S; ∗∗∗GLS-5300).