• Vaccine Name: INO-4800
• Target Pathogen: SARS-CoV-2
• Target Disease: COVID-19
• 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)
• Immunization Route: Intradermal injection (i.d.)
• Description: A DNA vaccine that expresses S protein from the pGX9501 vector(Smith 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: 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)