A Study to Evaluate Safety & Immunogenicity of SARS-CoV-2 DNA Vaccine Delivered Intramuscularly Followed by Electroporation for COVID-19

Summary

To investigate the safety and immunogenicity profile of of a novel and investigational SARS-CoV-2 DNA vaccine, which is delivered intramuscularly followed by electroporation to enhance vaccine penetration, as a potential prophylactic vaccine for current pandemic disease COVID-19.

Timeline

Start

2021-11-18

Primary completion

2022-06

Completion

2022-12

Publications

• Background SARS-CoV-2 DNA Vaccine - Investigator's Brochure (Version 1.0, Dated 24-Sep-2021).
• Background Alter G, Yu J, Liu J, Chandrashekar A, Borducchi EN, Tostanoski LH, McMahan K, Jacob-Dolan C, Martinez DR, Chang A, Anioke T, Lifton M, Nkolola J, Stephenson KE, Atyeo C, Shin S, Fields P, Kaplan I, Robins H, Amanat F, Krammer F, Baric RS, Le Gars M, Sadoff J, de Groot AM, Heerwegh D, Struyf F, Douoguih M, van Hoof J, Schuitemaker H, Barouch DH. Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans. Nature. 2021 Aug;596(7871):268-272. doi: 10.1038/s41586-021-03681-2. Epub 2021 Jun 9.
• Background Gallagher, K., Leick, M. B., Larson, R. C., Berger, T. R., Katsis, K., Yam, J. Y., Brini, G., Grauwet, K., MGH COVID-19 Collection & Processing Team, & Maus, M. V. (2021) 'SARS -CoV-2 T-cell immunity to variants of concern following vaccination', bioRxiv 2021.05.03.442455, Advance online publication. doi:10.1101/2021.05.03.442455.
• Background Liu C, Lu Z, Xie Y, Guo Q, Geng F, Sun B, Wu H, Yu B, Wu J, Zhang H, Yu X, Kong W. Soluble PD-1-based vaccine targeting MUC1 VNTR and survivin improves anti-tumor effect. Immunol Lett. 2018 Aug;200:33-42. doi: 10.1016/j.imlet.2018.06.004. Epub 2018 Jun 9.
• Background Martin JE, Sullivan NJ, Enama ME, Gordon IJ, Roederer M, Koup RA, Bailer RT, Chakrabarti BK, Bailey MA, Gomez PL, Andrews CA, Moodie Z, Gu L, Stein JA, Nabel GJ, Graham BS. A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. Clin Vaccine Immunol. 2006 Nov;13(11):1267-77. doi: 10.1128/CVI.00162-06. Epub 2006 Sep 20.
• Background Modjarrad K, Roberts CC, Mills KT, Castellano AR, Paolino K, Muthumani K, Reuschel EL, Robb ML, Racine T, Oh MD, Lamarre C, Zaidi FI, Boyer J, Kudchodkar SB, Jeong M, Darden JM, Park YK, Scott PT, Remigio C, Parikh AP, Wise MC, Patel A, Duperret EK, Kim KY, Choi H, White S, Bagarazzi M, May JM, Kane D, Lee H, Kobinger G, Michael NL, Weiner DB, Thomas SJ, Maslow JN. Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial. Lancet Infect Dis. 2019 Sep;19(9):1013-1022. doi: 10.1016/S1473-3099(19)30266-X. Epub 2019 Jul 24.
• Background Poland GA, Ovsyannikova IG, Kennedy RB. SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates. Lancet. 2020 Nov 14;396(10262):1595-1606. doi: 10.1016/S0140-6736(20)32137-1. Epub 2020 Oct 13.
• Background Sallberg M, Frelin L, Ahlen G, Sallberg-Chen M. Electroporation for therapeutic DNA vaccination in patients. Med Microbiol Immunol. 2015 Feb;204(1):131-5. doi: 10.1007/s00430-014-0384-8. Epub 2014 Dec 23.
• Background Tan Z, Chiu MS, Yan CW, Wong YC, Huang H, Man K, Chen Z. Antimesothelioma Immunotherapy by CTLA-4 Blockade Depends on Active PD1-Based TWIST1 Vaccination. Mol Ther Oncolytics. 2020 Feb 8;16:302-317. doi: 10.1016/j.omto.2020.01.009. eCollection 2020 Mar 27.
• Background Tan Z, Zhou J, Cheung AK, Yu Z, Cheung KW, Liang J, Wang H, Lee BK, Man K, Liu L, Yuen KY, Chen Z. Vaccine-elicited CD8+ T cells cure mesothelioma by overcoming tumor-induced immunosuppressive environment. Cancer Res. 2014 Nov 1;74(21):6010-21. doi: 10.1158/0008-5472.CAN-14-0473. Epub 2014 Aug 14.
• Background Tebas P, Roberts CC, Muthumani K, Reuschel EL, Kudchodkar SB, Zaidi FI, White S, Khan AS, Racine T, Choi H, Boyer J, Park YK, Trottier S, Remigio C, Krieger D, Spruill SE, Bagarazzi M, Kobinger GP, Weiner DB, Maslow JN. Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine - Preliminary Report. N Engl J Med. 2017 Oct 4:10.1056/NEJMoa1708120. doi: 10.1056/NEJMoa1708120. Online ahead of print.
• Background Tebas P, Yang S, Boyer JD, Reuschel EL, Patel A, Christensen-Quick A, Andrade VM, Morrow MP, Kraynyak K, Agnes J, Purwar M, Sylvester A, Pawlicki J, Gillespie E, Maricic I, Zaidi FI, Kim KY, Dia Y, Frase D, Pezzoli P, Schultheis K, Smith TRF, Ramos SJ, McMullan T, Buttigieg K, Carroll MW, Ervin J, Diehl MC, Blackwood E, Mammen MP, Lee J, Dallas MJ, Brown AS, Shea JE, Kim JJ, Weiner DB, Broderick KE, Humeau LM. Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: A preliminary report of an open-label, Phase 1 clinical trial. EClinicalMedicine. 2021 Jan;31:100689. doi: 10.1016/j.eclinm.2020.100689. Epub 2020 Dec 24.
• Background Wang P, Zheng M, Lau SY, Chen P, Mok BW, Liu S, Liu H, Huang X, Cremin CJ, Song W, Chen Y, Wong YC, Huang H, To KK, Chen Z, Xia N, Yuen KY, Chen H. Generation of DelNS1 Influenza Viruses: a Strategy for Optimizing Live Attenuated Influenza Vaccines. mBio. 2019 Sep 17;10(5):e02180-19. doi: 10.1128/mBio.02180-19.
• Background Wong YC, Liu W, Yim LY, Li X, Wang H, Yue M, Niu M, Cheng L, Ling L, Du Y, Chen SMY, Cheung KW, Wang H, Tang X, Tang J, Zhang H, Song Y, Chakrabarti LA, Chen Z. Sustained viremia suppression by SHIVSF162P3CN-recalled effector-memory CD8+ T cells after PD1-based vaccination. PLoS Pathog. 2021 Jun 14;17(6):e1009647. doi: 10.1371/journal.ppat.1009647. eCollection 2021 Jun.
• Background Vasan S, Hurley A, Schlesinger SJ, Hannaman D, Gardiner DF, Dugin DP, Boente-Carrera M, Vittorino R, Caskey M, Andersen J, Huang Y, Cox JH, Tarragona-Fiol T, Gill DK, Cheeseman H, Clark L, Dally L, Smith C, Schmidt C, Park HH, Kopycinski JT, Gilmour J, Fast P, Bernard R, Ho DD. In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. PLoS One. 2011;6(5):e19252. doi: 10.1371/journal.pone.0019252. Epub 2011 May 16.
• Background Vivarelli S, Falzone L, Torino F, Scandurra G, Russo G, Bordonaro R, Pappalardo F, Spandidos DA, Raciti G, Libra M. Immune-checkpoint inhibitors from cancer to COVID-19: A promising avenue for the treatment of patients with COVID-19 (Review). Int J Oncol. 2021 Feb;58(2):145-157. doi: 10.3892/ijo.2020.5159. Epub 2020 Dec 14.
• Background Yu Z, Tan Z, Lee BK, Tang J, Wu X, Cheung KW, Lo NT, Man K, Liu L, Chen Z. Antigen spreading-induced CD8+T cells confer protection against the lethal challenge of wild-type malignant mesothelioma by eliminating myeloid-derived suppressor cells. Oncotarget. 2015 Oct 20;6(32):32426-38. doi: 10.18632/oncotarget.5856.
• Background Zhou J, Cheung AK, Tan Z, Wang H, Yu W, Du Y, Kang Y, Lu X, Liu L, Yuen KY, Chen Z. PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice. J Clin Invest. 2013 Jun;123(6):2629-42. doi: 10.1172/JCI64704. Epub 2013 May 1.
• Background Development and Licensure of Vaccines to Prevent COVID-19 Guidance for Industry. U.S. Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research, June 2020

Drugs

Indications