ABSTRACT
Background DNA vaccines are safe, tolerable, elicit humoral and cellular responses, allow for repeated dosing over time, are thermostable at room temperature, and are easy to manufacture. We present a compilation of Phase 1 and Phase 2 data of Inovio’s US COVID-19 DNA Vaccine (INO-4800) targeting the full-length Spike antigen of SARS-CoV-2. A South Korean Phase 2 study is ongoing. Methods Participants in the open-label Phase 1 trial received 0.5 mg, 1.0 mg or 2.0 mg intradermally (ID) followed by electroporation (EP) at Days 0 and 28. An optional booster dose was administered >6 months post-dose 2. The Phase 2 further compared the 1.0 mg and 2.0 mg doses against placebo in a total of 401 participants randomized at a 3:3:1:1 ratio. ClinicalTrials.gov identifiers: NCT04336410 and NCT04642638 Results The majority of adverse events (AEs) related to INO-4800 across both trials were mild in severity and did not increase in frequency with age and subsequent doses. In Phase 1, 78% (14/18) and 84% (16/19) of subjects generated neutralizing antibody responses with geometric mean titers (GMTs) of 17.4 (95%CI 8.3, 36.5) and 62.3 (95% CI 36.4, 106.7) in the 1.0 and 2.0 groups, respectively (Figure 1). By week 8, 74% (14/19) and 100% (19/19) subjects generated T cell responses by Th1- associated IFNγ ELISPOT assay . Following a booster dose, neutralizing GMTs rose to 82.2 (95% CI 38.2, 176.9) and 124.7 (95% CI 62.8, 247.7) in the 1.0 mg and 2.0 mg groups, respectively, demonstrating the ability of INO-4800 to boost (Figure 2). In Phase 2, neutralizing antibody responses demonstrated GMTs of 93.6 (95%CI 77.3, 113.4) in the 1.0 mg dose group and 150.6 (95%CI 123.8, 183.1) in the 2.0 mg dose group (Figure 3). Conclusion INO-4800 appears safe and tolerable as a primary series and as a booster with the induction of both humoral and cellular immune responses. In addition to eliciting neutralizing antibodies, INO-4800 also induced T cell immune responses as demonstrated by IFNγ ELISpot. Finally, as a homologous booster, INO-4800, when administered 6-10.5 months following the primary series, resulted in an increased immune response without increase in reactogenicity. The 2.0 mg dose was selected for Phase 3 evaluation. Disclosures Joseph Agnes, PhD, Inovio (Employee, Shareholder) Mary Giffear, BS, Inovio Pharmaceuticals, Inc. (Employee) Kimberly A. Kraynyak, PhD, Inovio Pharmaceuticals (Employee, Other Financial or Material Support, Stock options) Dinah Amante, BS, Inovio (Employee) Emma Reuschel, PhD, Inovio Pharmaceuticals (Employee) Aaron Christensen-Quick, PhD, Inovio Pharmaceuticals, Inc (Employee) Viviane M. Andrade, PhD, Inovio Pharmaceuticals Inc. (Employee) Gabriella Garufi, PhD, Inovio Pharmaceuticals, Inc. (Employee) Albert Sylvester, MS, Inovio (Employee, Shareholder) Matthew P. Morrow, PhD, Inovio Pharmaceuticals (Employee) Patrick P. Pezzoli, BS, Inovio Pharmaceuticals, Inc. (Employee) Jan Pawlicki, PhD, Inovio Pharmaceuticals (Employee) Elisabeth Gillespie, PhD, Inovio Pharmaceuticals, Inc. (Employee) Katherine Schultheis, MSc, Inovio Pharmaceuticals (Employee) Hedieh Badie, PhD, INOVIO Pharmaceuticals (Employee) Timothy A. Herring, MPH, Inovio Pharmaceuticals, Inc. (Employee, Other Financial or Material Support, Own stock in the company) Keiko O. Simon, PhD, Inovio Pharmaceuticals (Employee) Trevor R. F. Smith, PhD, Inovio (Employee, Shareholder) Stephanie Ramos, PhD, Inovio Pharmaceuticals (Employee) Jessica Lee, MPH, Inovio Pharmaceuticals (Employee) Michael Dallas, PhD, Inovio Pharmaceuticals, Inc. (Employee, Shareholder) Ami Shah Brown, PhD, Abbot Laboratories (Shareholder)IBB Biotech ETF (Shareholder)Inovio Pharmaceuticals (Employee)J & J (Shareholder)Moderna (Shareholder) Jacqueline E. Shea, PhD, Inovio Pharmaceuticals (Employee, Shareholder) J Joseph Kim, PhD, Inovio (Employee) David Weiner, PhD, Inovio (Board Member, Grant/Research Support, Shareholder, I serve on the SAB in addition to the above activities) Kate Broderick, PhD, Inovio (Employee) Trevor Mc ullan, MSc, Inovio (Shareholder) Jean Boyer, PhD, Inovio (Employee) Laurent Humeau, PhD, Inovio Pharmaceuticals (Employee) Mammen P. Mammen Jr., MD, Inovio Pharmaceuticals (Employee)
ABSTRACT
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. IFNγ T cell responses were fully maintained against all variants tested.
ABSTRACT
Background: Additional SARS-CoV-2 vaccines that are safe and effective as both primary series and booster remain urgently needed to combat the COVID-19 pandemic. Here we describe the safety and durability of the immune response from two doses of a DNA vaccine (INO-4800) targeting the full-length Spike antigen and a subsequent homologous booster dose. Methods: INO-4800 was evaluated in 120 healthy participants across three dose groups (0.5 mg, 1.0 mg and 2.0 mg), each stratified by age. INO-4800 was injected intradermally followed by electroporation at 0 and 4 weeks followed by an optional booster dose 6-10.5 months following the second dose. Results: INO-4800 was well-tolerated, with no treatment-related serious adverse events reported. Most adverse events were mild in severity 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 detected in the 2.0 mg dose group. Conclusion: INO-4800 was well-tolerated as a 2-dose series and as a homologous booster dose in all adults, including the elderly. These results support further development of INO-4800 as a primary series and as a booster. Keywords: SARS-CoV-2; Clinical trial; DNA Vaccine; COVID-19; Immunogenicity; Booster
Subject(s)
COVID-19ABSTRACT
Background: Vaccines against SARS-CoV-2 are still urgently needed as only 5% of the global population has been vaccinated. Here we report the safety and immunogenicity of a DNA vaccine (INO-4800) targeting the full-length Spike antigen of SARS-CoV-2 when given to adults at high-risk of exposure. Methods: INO-4800 was evaluated in 401 participants randomized at a 3:3:1:1 ratio to receive either INO-4800 (1 mg or 2 mg dose) or placebo (1 or 2 injections) intradermally followed by electroporation (EP) using CELLECTRA 2000 at Days 0 and 28. ClinicalTrials.gov Identifier: NCT04642638 Findings: The majority of adverse events (AEs) were of Grade 1 and 2 in severity and did not appear to increase in frequency with the second dose. The number of participants experiencing each of the most common AEs did not differ appreciably between the two dosing groups. The geometric mean fold rise (GMFR) of binding and neutralizing antibody levels were statistically significantly greater in the 2.0 mg dose group versus the 1.0 mg dose group. The T cell immune responses measured by the ELISpot assay were also higher in the 2.0 mg dose group compared to the 1.0 mg dose group. Interpretation: INO-4800 at both the 1.0 mg and 2.0 mg doses when administered in a 2-dose regimen appeared to be safe and well-tolerated in all adult ages. However, the comparative immunogenicity analysis favored selection of INO-4800 2.0 mg dose for advancement into a Phase 3 efficacy evaluation. Funding: The Department of Defense, Joint Program Executive Office provided funding for the Phase 2 segment of the trial
ABSTRACT
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.
ABSTRACT
BACKGROUND: A vaccine against SARS-CoV-2 is of high urgency. Here the safety and immunogenicity induced by a DNA vaccine (INO-4800) targeting the full length spike antigen of SARS-CoV-2 are described. METHODS: 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. FINDINGS: The median age was 34.5, 55% (22/40) were men and 82.5% (33/40) white. 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. All 38 subjects evaluable for immunogenicity had cellular and/or humoral immune responses following the second dose of INO-4800. 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-É£ 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-É£ and TNF-α, without increase in IL-4. INTERPRETATION: INO-4800 demonstrated excellent safety and tolerability and was immunogenic in 100% (38/38) of the vaccinated subjects by eliciting either or both humoral or cellular immune responses. FUNDING: Coalition for Epidemic Preparedness Innovations (CEPI).