• Manufacturer: Academy of Military Science (AMS), Walvax Biotechnology, Suzhou Abogen Biosciences
• Vaccine Ontology ID: VO_0005161
• Type: mRNA vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Host Species as Laboratory Animal Model: mouse, cynomolgus monkeys
• Antigen: RBD domain of S protein (Zha, et al., 2020)
• Vector: Lipid nanoparticles (Zha, et al., 2020)
• Immunization Route: Intramuscular injection (i.m.)
• Storage: After treament can store
• Description: A SARS-CoV-2 mRNA vaccine made of lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2
  (Zha, et al., 2020)

• Product Name: PiCoVacc
• Manufacturer: Sinovac Biotech Ltd
• Vaccine Ontology ID: VO_0005142
• Type: Inactivated or "killed" vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Host Species as Laboratory Animal Model: Mouse, Macaque, Rat
• Antigen: Whole virus (Gao et al., 2020)
• Preparation: The virus was propagated in a 50-liter culture of Vero cells using the Cell Factory system and inactivated by using β-propiolactone The virus was purified using depth filtration and two optimized steps of chromatography, yielding a highly pure preparation of PiCoVacc. (Gao et al., 2020)
• Immunization Route: Intramuscular injection (i.m.)
• Description: A purified inactivated SARS-CoV-2 virus vaccine(Gao et al., 2020)

• Manufacturer: Inovio Pharmaceuticals
• Vaccine Ontology ID: VO_0005172
• Type: DNA vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Host Species as Laboratory Animal Model: mice, guinea pigs
• Antigen: S protein (Smith et al., 2020)
• Vector: pGX9501 plasmid (Smith et al., 2020)
• Immunization Route: Intradermal injection (i.d.)
• Description: A DNA vaccine that expresses S protein from the pGX9501 vector(Smith et al., 2020)

• Tradename: Covovax
• Manufacturer: Novavax
• Vaccine Ontology ID: VO_0005155
• CDC CVX code: 211
• CDC CVX description: SARS-COV-2 (COVID-19) vaccine, Subunit, recombinant spike protein-nanoparticle+Matrix-M1 Adjuvant, preservative free, 0.5mL per dose
• Type: Subunit vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Antigen: SARS-CoV-2 spike (S) glycoprotein (Keech et al., 2020)
• Immunization Route: Intramuscular injection (i.m.)
• Description: A recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. (Keech et al., 2020)

• Tradename: RBD-Dimer
• Vaccine Ontology ID: VO_0005142
• Type: Subunit vaccine
• Status: Clinical trial
• Host Species for Licensed Use: Human
• Host Species as Laboratory Animal Model: Mouse
• Immunization Route: Intramuscular injection (i.m.)
• Description: A SARS-CoV-2 vaccine made of an SARS-CoV-2 RBD-sc-dimer (Dai et al., 2020)

Human Response

• Vaccination Protocol: INO-4800 was evaluated in two groups of 20 participants, receiving either 1.0 mg or 2.0 mg of vaccine intradermally followed by CELLECTRA® EP at 0 and 4 weeks. Thirty-nine subjects completed both doses; one subject in the 2.0 mg group discontinued trial participation prior to receiving the second dose. ClinicalTrials.gov identifier: NCT04336410. (Tebas et al., 2020)
• Immune Response: By week 6, 95% (36/38) of the participants seroconverted based on their responses by generating binding (ELISA) and/or neutralizing antibodies (PRNT IC50), with responder geometric mean binding antibody titers of 655.5 [95% CI (255.6, 1681.0)] and 994.2 [95% CI (395.3, 2500.3)] in the 1.0 mg and 2.0 mg groups, respectively. For neutralizing antibody, 78% (14/18) and 84% (16/19) generated a response with corresponding geometric mean titers of 102.3 [95% CI (37.4, 280.3)] and 63.5 [95% CI (39.6, 101.8)], in the respective groups. By week 8, 74% (14/19) and 100% (19/19) of subjects generated T cell responses by IFN-ɣ ELISpot assay with the median SFU per 106 PBMC of 46 [95% CI (21.1, 142.2)] and 71 [95% CI (32.2, 194.4)] in the 1.0 mg and 2.0 mg groups, respectively. Flow cytometry demonstrated a T cell response, dominated by CD8+ T cells co-producing IFN-ɣ and TNF-α, without increase in IL-4. (Tebas et al., 2020)
• Side Effects: Through week 8, only 6 related Grade 1 adverse events in 5 subjects were observed. None of these increased in frequency with the second administration. No serious adverse events were reported. (Tebas et al., 2020)

Mouse Response

• Vaccination Protocol: Female BALB/c mice were immunized i.m. with 2 μg (n = 8) or 10 μg (n = 8) of ARCoV or a placebo (n = 5) and boosted with an equivalent dose 14 days later. Serum was collected 7, 14, 21, and 28 days after initial vaccination. (Zhang et al., 2020)
• Immune Response: Remarkably, a second immunization with 2 or 10 μg of ARCoV mRNA-LNP resulted in rapid elevation of immunoglobulin G (IgG) and neutralizing antibodies in mice, whereas no SARS-CoV-2-specific IgG and neutralizing antibodies were detected in sera from mice vaccinated with empty LNPs. 28 days after initial immunization, the NT50 titers in mice immunized with 2 or 10 μg of ARCoV mRNA-LNP approached ∼1/2,540 and ∼1/7,079, respectively, and the PRNT50 reached ∼1/2,194 and ∼1/5,704, respectively. (Zhang et al., 2020)
  There was a significant increase in virus-specific CD4+ and CD8+ effector memory T (Tem) cells in splenocytes from ARCoV-vaccinated mice in comparison with placebo LNPs (Figure 4 A) upon stimulation with peptide pools covering the SARS-CoV-2 RBD. Secretion of interferon γ (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-2 (IL-2) in splenocytes from mRNA-LNP-immunized mice was significantly higher than in those that received the placebo vaccination. There was no significant difference in IL-4 and IL-6 secretion between ARCoV-immunized animals and placebo-immunized ones, demonstrating that the mRNA-LNP vaccine successfully induces a Th1-biased, SARS-CoV-specific cellular immune response. (Zhang et al., 2020)
• Challenge Protocol: Mice that received two doses of immunization of ARCoV mRNA-LNP at 2 or 10 μg were challenged i.n. with 6,000 plaque-forming units (PFUs) of SARS-CoV-2 MASCp6 40 days after initial vaccination. (Zhang et al., 2020)
• Efficacy: All mice immunized with 2 or 10 μg of ARCoV mRNA-LNP showed full protection against SARS-CoV-2 infection, and no measurable viral RNA was detected in the lungs and trachea , whereas high levels of viral RNA were detected in the lungs and trachea (∼109 and 107 RNA copy equivalents per gram, respectively) of mice in the placebo group. (Zhang et al., 2020)

Mouse Response

• Host Strain: BALB/c mouse
• Vaccination Protocol: Mice were vaccinated at day 0 and 7 with either 1.5 μg/dose, 3.0 μg/dose, or 6.0 μg/dose on both days. (Gao et al., 2020)
• Immune Response: SARS-CoV-2 S- and RBD-specific immunoglobulin G (Ig G) developed quickly in the serum of vaccinated mice and peaked at the titer of 819,200 (>200 μg/ml) and 409,600 (>100 μg/ml), respectively, at week 6(Gao et al., 2020)
• Description: BALB/c mice were injected with vaccine 5761 at days 0 and 7.(Gao et al., 2020)

Mouse Response

• Vaccination Protocol: BALB/c mice were immunized twice with 10 micrograms of INO-4800, on days 0 and 14, and sera was collected on day 7 post-second immunization. (Smith et al., 2020)
• Immune Response: Neutralization ID50 average titers of 92.2 were observed in INO-4800 immunized mice. No reduction in RLU (relative luciferase units) was observed for the control animals. Sera from INO-4800 immunized BALB/c mice neutralized both SARS-CoV-2/WH-09/human/2020 and SARS-CoV-2/Australia/VIC01/2020 virus strains with average ND50 titers of 97.5 and 128.1, respectively. Sera from INO-4800 immunized C57BL/6 mice neutralized wildtype SARS-CoV-2 virus with average ND50 titer of 340. Inhibition of the Spike-ACE2 interaction was compared using serum IgG from a naïve mouse and from an INO-4800 vaccinated mouse. The receptor inhibition assay was repeated with a group of five immunized mice, and demonstrating that INO-4800-induced antibodies competed with ACE2 binding to the SARS-CoV-2 Spike protein. (Smith et al., 2020) Flow cytometric analysis on splenocytes harvested from BALB/c mice on Day 14 after a single INO-4800 immunization revealed the T cell compartment to contain 0.04% CD4+ and 0.32% CD8+ IFN-γ+ T cells after stimulation with SARS-CoV-2 antigens. (Smith et al., 2020) CoV vaccine-induced immunopathology utilized the BALB/c mouse, a model known to preferentially develop Th2-type responses. The DNA vaccine platform induces Th1-type immune responses and has demonstrated efficacy without immunopathology in models of respiratory infection. (Smith et al., 2020)

Mouse Response

• Vaccination Protocol: Groups of mice were immunized with a dose range (0.01 μg, 0.1 μg, 1 μg, and 10 μg) of NVX-CoV2373 with 5 μg Matrix-M adjuvant using a single priming dose or a prime/boost regimen spaced 14 days apart. (Tian et al., 2021)
• Immune Response: Animals immunized with a single priming dose of 0.1–10 μg NVX-CoV2373/Matrix-M had elevated anti-S IgG titers that were detected 21–28 days after a single immunization. Mice immunized with 10 μg NVX-CoV2373/Matrix-M induced antibodies that blocked hACE2 receptor binding to S-protein and virus neutralizing antibodies 21–28 days after a single priming dose. Animals immunized with the prime/boost regimen had significantly elevated anti-S IgG titers that were detected 7–16 days following the booster immunization across all dose levels. Animals immunized with 1 μg and 10 μg NVX-CoV2373/Matrix-M had similar high anti-S IgG titers following immunization (geometric mean titer, GMT = 139,000 and 84,000, respectively). Importantly, mice immunized with 0.1 μg, 1 μg, or 10 μg NVX-CoV/Matrix-M had significantly (p ≤ 0.00006) higher anti-S IgG titers compared to mice immunized with 10 μg NVX-CoV2373 without adjuvant. Immunization with two doses of NVX-CoV2373/Matrix-M elicited high titer antibodies that blocked hACE2 receptor binding to S-protein (IC50 = 218–1642) and neutralized the cytopathic effect (CPE) of SARS-CoV-2 on Vero E6 cells (100% blocking of CPE = 7680–20,000) across all dose levels. (Tian et al., 2021)
• Challenge Protocol: Mice were immunized with a single priming dose or a prime/boost regimen with NVX-CoV2373/Matrix-M as described above. Since mice do not support replication of WT SARS-CoV-2 virus, BALB/c mice were transduced with adenovirus encoding human ACE2 receptor (Ad/hACE2) which renders them permissive to infection with SARS-CoV-2 (refs. 21,22). At 4 days post transduction, mice were challenged with 105 plaque forming units (pfu)/mouse of SARS-CoV-2 (WA1 strain). Following challenge, mice were weighed daily and pulmonary histology and viral load were analyzed at 4 and 7 days post challenge. (Tian et al., 2021)
• Efficacy: At 4 days post infection (dpi), placebo-treated mice had an average of 104 SARS-CoV-2 pfu/lung, while the mice immunized with NVX-CoV2373 without Matrix-M had 103 pfu/lung and those with Matrix-M had limited to no detectable virus load. The NVX-CoV2373 with Matrix-M prime-only groups of mice exhibited a dose-dependent reduction in virus titer, with recipients of the 10 μg dose having no detectable virus at day 4 post infection. Mice receiving 1 μg, 0.1 μg, and 0.01 μg doses all showed a marked reduction in titer compared to placebo-vaccinated mice. In the prime/boost groups, mice immunized with 10 μg, 1 μg, and 0.1 μg doses had almost undetectable lung virus loads. These results confirmed that NVX-CoV2373 confers protection against SARS-CoV-2 and that low doses of the vaccine associated with lower serologic responses do not exacerbate weight loss or induce exaggerated illness. (Tian et al., 2021)

Mouse Response

• Host Strain: Balb/c
• Vaccination Protocol: Mice were immunized by subcutaneous injection with 50 μg of RBD-CuMVTT ((Zha, et al., 2020))
• Immune Response: Induced neutralizing antibodies, production of RBD-Specific antibodies ((Zha, et al., 2020))

Rat Response

• Host Strain: Wistar
• Vaccination Protocol: Rats were vaccinated at day 0 and 7 with either 1.5 μg/dose, 3.0 μg/dose, or 6.0 μg/dose on both days.(Gao et al., 2020)
• Immune Response: Immune Response Description: SARS-CoV-2 S- and RBD-specific immunoglobulin G (Ig G) developed quickly in the serum of vaccinated rats and the maximum neutralizing titers reached 2,048-4,096 at week 7 (Gao et al., 2020)

Macaque Response

• Vaccination Protocol: Two groups of macaques (n = 10/group) were immunized with 100 or 1,000 μg of ARCoV mRNA-LNP via i.m. administration and boosted with the same dose 14 days after initial immunization. The same number of monkeys (n = 10) was vaccinated with PBS as a placebo. (Zhang et al., 2020)
• Immune Response: specific IgG antibodies were readily induced on day 14 after initial immunization, and the booster immunization resulted in a notable increase in IgG titers to ∼1/5,210 and ∼1/22,085 on day 28 after initial immunization. Fifty percent of animals that received high-dose ARCoV immunization developed low-level neutralizing antibodies on day 14 after initial immunization, whereas the booster immunization resulted in a notable increase in NT50 to ∼1/699 and ∼1/6,482 in monkeys vaccinated with low- or high-dose ARCoV, respectively. SARS-CoV-2 RBD-specific T cell responses were stimulated in peripheral blood monocytes (PBMCs) from monkeys vaccinated with a low or high dose of ARCoV on day 5 after booster immunization but not from animals receiving a placebo. There was no significant difference in IL-4+/CD4+ cell response to the SARS-CoV-2 RBD between ARCoV- and placebo-treated animals, suggesting induction of a Th1-biased cellular immune response by ARCoV immunization. (Zhang et al., 2020)

Macaque Response

• Host Strain: Rhesus macaque
• Vaccination Protocol: Macaques were immunized three times via the intramuscular route with medium (3 μg per dose) or high doses (6 μg per dose) of PiCoVacc at day 0, 7 and 14 (n=4)(Gao et al., 2020)
• Immune Response: . S-specific IgG and NAb were induced at week 2 and rose to ~12,800 and ~50, respectively at week 3 after vaccination in both vaccinated groups, whose titers are similar to those of serum from the recovered COVID-19 patients. NAb titer (61) in the medium dose immunized group were ~20% greater than that observed (50) in the high dose vaccinated group at week 3, removing the outlier instead have medium dose group be ~40% lower than that in the high dose group (Gao et al., 2020)
• Side Effects: No serious pathology recorded at day 29 in vaccinated groups (Gao et al., 2020)
• Challenge Protocol: Challenge protocol involved direct inoculation of 1e6 TCID50 of SARS-CoV-2 CN1 into the animal lung through the intratracheal route at day 22 (one week after the third immunization and after immune response results were recorded) (Gao et al., 2020).
• Efficacy: argely protected against SARS-CoV-2 infection with very mild and focal histopathological changes in a few lobes of lung, which probably were caused by a direct inoculation of 106 TCID50 of virus into the lung through intratracheal route, that needed longer time (more than one week) to recover completely (Gao et al., 2020).