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

Pablo Tebas, Shu Ping Yang, Jean D. Boyer, Emma L. Reuschel, Ami Patel, Aaron Christensen-Quick, Viviane M. Andrade, Matthew P. Morrow, Kimberly Kraynyak, Joseph Agnes, Mansi Purwar, Albert Sylvester, Jan Pawlicki, Elisabeth Gillespie, Igor Maricic, Faraz I. Zaidi, Kevin Y. Kim, Yaya Dia, Drew Frase, Patrick PezzoliKatherine Schultheis, Trevor R.F. Smith, Stephanie J. Ramos, Trevor McMullan, Karen Buttigieg, Miles Carroll, John Ervin, Malissa C. Diehl, Elliott Blackwood, Mammen P. Mammen, Jessica Lee, Michael J. Dallas, Ami Shah Brown, Jacqueline E. Shea, J. Joseph Kim, David B. Weiner, Kate E. Broderick, Laurent M. Humeau*

*Corresponding author for this work

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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 (R) 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-gamma 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-gamma and TNF-alpha, 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. 

Original languageEnglish
Article number100689
Number of pages9
JournalEClinicalMedicine
Volume31
Early online date24 Dec 2020
DOIs
Publication statusPublished - Jan 2021

Bibliographical note

Funding Information: SY, JDB, ACQ, VMA, MPM, KK, JA, AS, JP, EG, IM, PP, KS, TRFS, SR, TMcM, MD, EB, MPM, JL, MD, ASB, JES, JJK, KEB and LMH report grants from Coalition for Epidemic Preparedness Innovations, during the conduct of the study; other from Inovio Pharmaceuticals, outside the submitted work. PT, ELR, AP, MP, FIZ, KYK, YD, DF, KB, MWC, JE and DBW report grants from Coalition for Epidemic Preparedness Innovations, during the conduct of the study.
This work is funded by Coalition for Epidemic Preparedness Innovations (CEPI).

Open Access: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Publisher Copyright: Crown Copyright © 2020 Published by Elsevier Ltd

Citation: Pablo Tebas, ShuPing Yang, Jean D. Boyer, Emma L. Reuschel, Ami Patel, Aaron Christensen-Quick, Viviane M. Andrade, Matthew P. Morrow, Kimberly Kraynyak, Joseph Agnes, Mansi Purwar, Albert Sylvester, Jan Pawlicki, Elisabeth Gillespie, Igor Maricic, Faraz I. Zaidi, Kevin Y. Kim, Yaya Dia, Drew Frase, Patrick Pezzoli, Katherine Schultheis, Trevor R.F. Smith, Stephanie J. Ramos, Trevor McMullan, Karen Buttigieg, Miles W. Carroll, John Ervin, Malissa C. Diehl, Elliott Blackwood, Mammen P. Mammen, Jessica Lee, Michael J. Dallas, Ami Shah Brown, Jacqueline E. Shea, J.Joseph Kim, David B. Weiner, Kate E. Broderick, Laurent M. Humeau, Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: A preliminary report of an open-label, Phase 1 clinical trial, EClinicalMedicine, Volume 31, 2021, 100689, ISSN 2589-5370.

DOI: https://doi.org/10.1016/j.eclinm.2020.100689.

Keywords

  • COVID-19
  • DNA vaccine
  • INO-4800
  • Phase 1
  • SARS-CoV-2
  • EFFICACY

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