SARS-CoV-2 DNA Vaccine INO-4800 Induces Durable Immune Responses Capable of Being Boosted in a Phase 1 Open-Label Trial

BackgroundAdditional SARS-CoV-2 vaccines that are safe and effective as primary vaccines and boosters remain urgently needed to combat the COVID-19 pandemic. We describe the safety and durability of the immune responses following two primary doses and a homologous booster dose of an investigational DNA vaccine (INO-4800) targeting the full-length spike antigen. MethodsThree dosage strengths of INO-4800 (0.5 mg, 1.0 mg, and 2.0 mg) were evaluated in 120 age-stratified healthy adults. Intradermal injection of INO-4800 followed by electroporation at 0 and 4 weeks preceded an optional booster 6-10.5 months after the second dose. ResultsINO-4800 appeared well tolerated, with no treatment-related serious adverse events. Most adverse events were mild and did not increase in frequency with age and subsequent dosing. A durable antibody response was observed 6 months following the second dose; a homologous booster dose significantly increased immune responses. Cytokine producing T cells and activated CD8+ T cells with lytic potential were significantly increased in the 2.0 mg dose group. ConclusionINO-4800 was well tolerated in a 2-dose primary series and as a homologous booster in all adults, including the elderly. These results support further development of INO-4800 for use as a primary vaccine and as a booster. Trial Registration: ClinicalTrials.gov NCT04336410 SummaryTwo-milligram dose of INO-4800, a DNA-based vaccine encoding the SARS-CoV-2 spike protein, appears safe and well-tolerated and elicits humoral and cell-mediated immunity persisting to 6 months after a second dose. A third dose 6-10.5 months later significantly boosts immune responses.

INO-4800 DNA Vaccine Induces Neutralizing Antibodies and T cell Activity Against Global SARS-CoV-2 Variants

Global surveillance has identified emerging SARS-CoV-2 variants of concern (VOC) associated with broadened host specificity, pathogenicity, and immune evasion to vaccine induced immunity. Here we compared humoral and cellular responses against SARS-CoV-2 VOC in subjects immunized with the DNA vaccine, INO-4800. INO-4800 vaccination induced neutralizing antibodies against all variants tested, with reduced levels detected against B.1.351. IFN{gamma} T cell responses were fully maintained against all variants tested.