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

EClinicalMedicine

John Ervin¹  Pablo Tebas²  Jean D. Boyer³  ShuPing Yang³  Katherine Schultheis³  Malissa C. Diehl³  Albert Sylvester³  Michael J. Dallas³  Elliott Blackwood³  Jacqueline E. Shea³  Laurent M. Humeau³  Aaron Christensen-Quick³  Patrick Pezzoli³  Kimberly Kraynyak³  Viviane M. Andrade³  Elisabeth Gillespie³  Ami Shah Brown³  Kate E. Broderick³  Joseph Agnes³  Jessica Lee³  Jan Pawlicki³  Mammen P. Mammen³  Igor Maricic³  Trevor R.F. Smith³  Trevor McMullan³  Stephanie J. Ramos³  Matthew P. Morrow³  J.Joseph Kim³  Karen Buttigieg⁴  Miles W. Carroll⁴  Faraz I. Zaidi⁵  Ami Patel⁵  Emma L. Reuschel⁵  Drew Frase⁵  Mansi Purwar⁵  David B. Weiner⁵  Yaya Dia⁵  Kevin Y. Kim⁵ 

[1] Alliance for Multispecialty Research, Kansas City, MO 64114-4866;Hospital of the University of Pennsylvania, Philadelphia, PA, USA;Inovio Pharmaceuticals, Plymouth Meeting, PA 19462, USA;Public Health England, Porton, United Kingdom;Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, PA 19104, USA;

关键词: SARS-CoV-2;    COVID-19;    DNA vaccine;    INO-4800;    Phase 1;   

DOI  :  

来源: DOAJ

【 摘 要 】

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-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).

【 授权许可】

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