Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: a preliminary report of a randomized, blinded, placebo-controlled, Phase 2 clinical trial in adults at high risk of viral exposure
Authors: Mammen Mammen P. , Tebas Pablo , Agnes Joseph , Giffear Mary , Kraynyak Kimberly A. , Blackwood Elliott , Amante Dinah , Reuschel Emma L. , Purwar Mansi , Christensen-Quick Aaron , Liu Nieman , Andrade Viviane M. , Carter Julie , Garufi Gabriella , Diehl Malissa C. , Sylvester Albert , Morrow Matthew P. , Pezzoli Patrick , Kulkarni Abhijeet J. , Zaidi Faraz I. , Frase Drew , Liaw Kevin , Badie Hedieh , Simon Keiko O. , Smith Trevor R.F. , Ramos Stephanie , Spitz Robert , Juba Robert J. , Lee Jessica , Dallas Michael , Brown Ami Shah , Shea Jacqueline E. , Kim J. Joseph , Weiner David B. , Broderick Kate E. , Boyer Jean D. , Humeau Laurent M. 
Published: May 2021

AbstractBackgroundVaccines 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.MethodsINO-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 (ID) followed by electroporation (EP) using CELLECTRA® 2000 at Days 0 and 28. ClinicalTrials.gov Identifier:NCT04642638FindingsThe 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.InterpretationINO-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.FundingThe trial was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, (JPEO-CBRND) in coordination with the Office of the Assistant Secretary of Defense for Health Affairs (OASD(HA)) and the Defense Health Agency.Research in contextINO-4800 is among several vaccines being tested against SARS-CoV-2, the virus that causes COVID-19 with the goal of inducing a protective immune response. The DNA vaccine, INO-4800, administered by ID injection followed by electroporation (EP) using the CELLECTRA®2000 device, induces a balanced immune response that includes engagement of both T cells and B1-5.Added value of this studyThis is the first report of a randomized, blinded, placebo-controlled clinical trial of INO-4800, a DNA vaccine targeting the SARS-CoV-2 Spike antigen delivered ID followed by EP, in adults at high risk of SARS-CoV-2 exposure.