Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: A preliminary report of an open-label, Phase 1 clinical trial

Type Journal Article Author Pablo Tebas Author ShuPing Yang Author Jean D. Boyer Author Emma L. Reuschel Author Ami Patel Author Aaron Christensen-Quick Author Viviane M. Andrade Author Matthew P. Morrow Author Kimberly Kraynyak Author Joseph Agnes Author Mansi Purwar Author Albert Sylvester Author Jan Pawlicki Author Elisabeth Gillespie Author Igor Maricic Author Faraz I. Zaidi Author Kevin Y. Kim Author Yaya Dia Author Drew Frase Author Patrick Pezzoli Author Katherine Schultheis Author Trevor R. F. Smith Author Stephanie J. Ramos Author Trevor McMullan Author Karen Buttigieg Author Miles W. Carroll Author John Ervin Author Malissa C. Diehl Author Elliott Blackwood Author Mammen P. Mammen Author Jessica Lee Author Michael J. Dallas Author Ami Shah Brown Author Jacqueline E. Shea Author J. Joseph Kim Author David B. Weiner Author Kate E. Broderick Author Laurent M. Humeau URL https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30433-8/abstract Volume 31 Publication EClinicalMedicine | The Lancet ISSN 2589-5370 Date 23/12/2020 Extra Publisher: Elsevier PMID: 33392485 Journal Abbr EClinicalMedicine DOI 10.1016/j.eclinm.2020.100689 Library Catalog www.thelancet.com Language English 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. • View related content for this article 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-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. 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). Short Title Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2