Table 1.
Candidate vaccines in various clinical evaluations towards COVID-19.
| Candidate vaccine | Type | Status | Description | References |
|---|---|---|---|---|
| Ad5-nCoV (NCT04313127) | Non-replicating viral vector | Phase II Clinical trial |
Ad5-nCoV is a genetically engineered vaccine that uses the replication-defective adenovirus type 5 as the vector to display S protein(s) of SARS-CoV-2. It is designed to block the COVID-19. | [142] |
| ChAdOx1 nCoV-19 (AZD1222) (NCT04324606) | Non-replicating viral vector | Ongoing to Phases II clinical trial | hAdOx1 nCoV-19 is generated from a virus (ChAdOx1), a weakened form of a chimpanzee’s adenovirus that has been genetically modified so that it cannot grow in humans. A genetic element has been incorporated into the ChAdOx1 construct to produce S proteins of the SARS-CoV-2. This protein is commonly located outside of the SARS-CoV-2, and has a vital role in SARS-CoV-2 pathogenesis. | [143] |
| mRNA-1273 (NCT04283461) | RNA vaccine | Phase I clinical trial | mRNA-1273 is an mRNA vaccine against SARS-CoV-2 coding for a prefusion-stabilized form of the S protein. Consistent with the antibody data, mRNA-1273 vaccination elicited neutralizing antibodies in participants. | [144] |
| INO-4800 (NCT04336410) | DNA Vaccine | Phase I clinical trial | INO-4800 has induced robust neutralizing antibodies and T cell immune responses in preclinical models. Participants experienced one ID injection of 1.0 mg INO-4800. The engineered construct, INO-4800, results in S protein expression. | [145] |
| LV-SMENP-DC vaccine (NCT04276896) | Modified APC | Phase II clinical trial | Based on the genomic sequence of the novel coronavirus, conserved and essential structural and protease protein domains have been chosen to engineer lentiviral SMENP minigenes to express COVID-19 antigens. -SMENP-DC vaccine is made by the modification of DC with lentivirus vectors displaying COVID-19 minigene SMENP and immune-modulatory genes. CTLs are stimulated by LV-DC, which presents COVID-19 specific antigens. | [146] |
| COVID-19/aAPC vaccine (NCT04299724) | Engineered lentiviral minigenes (Modified APC) | Phase I clinical trial | Based on the genomic sequence of SARS-CoV-2, conserved and necessary structural and protease protein domains are selected to engineer lentiviral minigenes for SARS-CoV-2 antigen expression. The COVID-19/aAPC vaccine is prepared by lentiviral modifications, including immune-modulatory genes and the viral minigenes to the artificial antigen-presenting cells (aAPCs). | [119] |
| Bacille Calmette-Guerin (NCT04328441) | Other | Phase III/IV clinical trial | The Bacille Calmette-Guerin is a live attenuated vaccine comprised of the causative agent of bovine tuberculosis (Mycobacterium bovis). Amazingly, BCG vaccination seems to not only protect humans against severe childhood tuberculosis but has non-specific protective effects against other respiratory tract infections both in vitro and in vivo. Thus, this vaccine is being repurposed to see whether it can diminish morbidity and mortality correlated with SARS-CoV-2 infection. | [120] |
| AV-COVID-19 (NCT04386252) | Modified APC | Phase I/II clinical trial | The AV-COVID-19 vaccine is obtained from autologous dendritic cells (DC) loaded with antigens from the SARS-CoV-2 to prevent COVID-19. To produce this vaccine, monocytes of a healthy individual will be isolated. These monocytes will be differentiated into DCs using IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) followed by incubation with SARS-CoV-2 antigens to create AV-COVID-19. This vaccine will be administered subcutaneously with or without extra GM-CSF. | [147] |
| SARS-CoV-2 rS (NCT04368988) | Protein subunit | Phase I clinical trial | The SARS-CoV-2 rS vaccine is an intramuscularly administered nanoparticle vaccine. The nanoparticles are designed by infecting Sf9 insect cells with baculoviruses vectors that express the SARS-CoV-2 S protein. The proteins are correctly folded, undergo a series of programmed modifications, and are eventually transferred to the cell surface. Correctly folded and modified S proteins are then extracted from the cell surface and purified to preserve their three-dimensional structure and biological function, ultimately serving as the immunogenic molecules in the vaccine. The vaccine is also being tested with Matrix M adjuvant. This saponin-based adjuvant acts in part by stimulating the entry of antigen-presenting cells into the injection site and intensifying antigen presentation in the local lymph nodes. | [148] |
| bacTRL-Spike (NCT04334980) | DNA-based | Phase I clinical trial | bacTRL-Spike-1 is an oral vaccine containing live Bifidobacterium longum, which has been modified to deliver plasmids containing synthetic DNA coding for S proteins of SARS-CoV-2 to human cells. These S proteins can then induce immune responses. | [149] |
| V-SARS (NCT04380532) | Inactivated virus | Phase I/II clinical trial | The V-SARS vaccine is made from the heat-inactivated plasma of donors with COVID-19. The idea behind this vaccine is that individuals with COVID-19 will have to circulate SARS-CoV-2. Thus, heat-inactivation of their plasma will efficiently deliver an inactived virus to healthy individuals, inducing an immune response against this pathogen. This vaccine will be administered orally in pill form. | [150] |
| BNT162 (a1, b1, b2, c2) (EudraCT 2020001038-36) | RNA-based vaccine | Phase I/II clinical trial | The BNT162 vaccine trial is comprised of four (a1, b1, b2, and c2) prophylactic SARS-CoV-2 RNA vaccines against COVID-19. Two candidates are the modified nucleoside mRNA (modRNA), one is uridine-containing mRNA (uRNA), and the other candidate is the self-amplifying mRNA (saRNA). These first two vaccines are the spike sequences from SARS-CoV-2, and the other two are only the receptor-binding domain (RBD) sequences. | [151] |
| SARS-CoV-2 inactivated vaccine (Unnamed Candidate) (ChiCTR2000031809) | Inactivated virus | Phase I/II clinical trial | Inactive viral vaccines are generated by multiplying viruses in cell culture (such as in Vero cells) followed by inactivation with a chemical reagent (such as beta-propiolactone). Upon vaccination, this allows the body to induce diverse immune responses against various viral antigens while having no threat of actually being infective. | [152] |
| Measles-Mumps-Rubella Vaccine (NCT04357028) | Other | Phase III clinical trial | The measles-mumps-rubella (MMR) vaccine is composed of live-attenuated viruses. This vaccination is a safe and effective way to prevent these infections, especially in young children. Interestingly, young children do not seem to be overly susceptible to COVID-19. One hypothesis is that antibodies against measles (due to the MMR vaccine) may be cross-reactive with SARS-CoV-2. Thus, vaccination with the MMR vaccine may be protective against COVID-19. | [153] |
| DPX-COVID-19 | protein subunit, lipid-based delivery | Preclinical Phase | DPX is the company’s established lipid-based delivery platform with no aqueous elements in the final formulation. The DPX platform can be formulated with peptide antigens. Its unique “no release” mechanism of action allows antigen-presenting cells (APCs) to be attracted to the injection site, facilitating a robust and sustained immune response within the lymph nodes. This patented technology leverages a novel mechanism of action that allows the in vivo programming of immune cells, which is directed at producing potent new synthetic therapeutics. IMV’s lead candidate, DPX-Survivac, is a T cell-activating immunotherapy combined with survivin. IMV is currently evaluating DPX-Survivac in advanced ovarian cancer, as well as in combination therapy in various clinical studies with Merck’s Keytruda®. IMV is also developing a DPX-based vaccine to combat COVID-19. | [154] |
| LUNAR-COV19 | RNA, mRNA | Preclinical Phase | Low dosage, single-shot, self-replicating mRNA vaccine lacks viral elements or co-adjuvants. The vaccine is based on STARR™ (Self-Transcribing And Replicating RNA), which combines self-replicating RNA with LUNAR® (Lipid-enabled and Unlocked Nucleomonomer Agent modified RNA) lipid-mediated delivery system into a single solution to generate proteins inside the human body. | [154] |
| CureVac | RNA-based vaccine | Preclinical Phase | CureVac proclaimed a positive pre-clinical outcome at a low dose for its lead vaccine candidate against SARS-CoV-2. Its leading vaccine candidate for coronavirus has generated a high level of virus-neutralizing titers after 2 µg dose of vaccination in pre-clinical investigations. CureVac has demanded started the clinical trial Phase 1/2a in June 2020. | [154] |
| PittCoVacc | Protein subunit | Preclinical Phase | PittCoVacc vaccine is an elementary protein vaccine made from a small fragment of one of the viral proteins. It uses a process similar to that in seasonal flu shots. They also leveraged a new method called a microneedle array to deliver the drug for increasing the potency of the vaccine. | [154] |
| AdCOVID | Non-replicating viral vector | Preclinical Phase | The COVID-19 vaccine, named AdCOVID, is a single-dose vaccine candidate that is delivered by an intranasal spray and is designed to activate several components of the immune system including humoral (antibodies), cellular (T-cell) and mucosal immunity. | [154] |
| CoroFlu | Inactivated virus | Preclinical Phase | An intranasal vaccine for coronavirus, ‘CoroFlu’ is under progress. CoroFlu is built on the backbone of FluGen’s flu vaccine candidate known as M2SR. The research group will insert gene sequences from SARS-CoV-2 into M2SR so that the new vaccine will induce immunity against this virus. CoroFlu will also display the influenza virus hemagglutinin protein, which is the dominant influenza virus antigen, so that immune responses will be induced against both coronavirus and influenza (H2N2 seasonal flu strain). | [154] |