Phase-I Study to Evaluate the Safety and Immunogenicity of a Prophylactic pDNA Vaccine Candidate Against COVID-19 in Healthy Adults

Summary

A pneumonia of unknown cause detected in Wuhan, China, was first reported in December 2019. On 08 January 2020, the pathogen causing this outbreak was identified as a novel coronavirus 2019. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. On 12 February 2020, the virus was officially named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the WHO officially named the disease caused by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). On 11 March 2020, the WHO upgraded the status of the COVID-19 outbreak from epidemic to pandemic, which is now spreading globally at high speed. There are currently few licensed vaccines to prevent infection with SARS-CoV-2 or COVID-19 and the duration of response is unknown. Given the rapid transmission of COVID-19 and incidence of disease on a worldwide basis, the rapid development of effective vaccines with sufficient protection and duration of response is of utmost importance. IAU has developed a thermally stable plasmid DNA (pDNA)-based vaccine candidate using a platform approach that enables the rapid development of vaccines against emerging viral diseases, including SARS-CoV-2. The pDNA vaccine developed by IAU is a synthetic, codon-optimized, encode either the full-length Spike (S) gene or S1 domain of SARS-CoV-2 as genes of interest. Here, we aim to test a synthetic, codon optimized pDNA encoding S.opt.FL as vaccine candidate against COVID-19. A key advantage of pDNA vaccine is that multiple immunization can be used without the limitations of anti-vector responses. This study is intended to investigate the safety, immunogenicity, and tolerbilty of this prophylactic vaccine against COVID-19 administered as intramuscular immunization (i.m.).

Timeline

Start

2022-11-20

Primary completion

2023-03-01

Completion

2023-07-01

Publications

• Background Viner RM, Ward JL, Hudson LD, Ashe M, Patel SV, Hargreaves D, Whittaker E. Systematic review of reviews of symptoms and signs of COVID-19 in children and adolescents. Arch Dis Child. 2021 Jul 19;106(8):802-807. doi: 10.1136/archdischild-2020-320972.
• Background Chen X, Laurent S, Onur OA, Kleineberg NN, Fink GR, Schweitzer F, Warnke C. A systematic review of neurological symptoms and complications of COVID-19. J Neurol. 2021 Feb;268(2):392-402. doi: 10.1007/s00415-020-10067-3. Epub 2020 Jul 20.
• Background Oliver SE, Gargano JW, Marin M, Wallace M, Curran KG, Chamberland M, McClung N, Campos-Outcalt D, Morgan RL, Mbaeyi S, Romero JR, Talbot HK, Lee GM, Bell BP, Dooling K. The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Moderna COVID-19 Vaccine - United States, December 2020. MMWR Morb Mortal Wkly Rep. 2021 Jan 1;69(5152):1653-1656. doi: 10.15585/mmwr.mm695152e1.
• Background Oliver SE, Gargano JW, Marin M, Wallace M, Curran KG, Chamberland M, McClung N, Campos-Outcalt D, Morgan RL, Mbaeyi S, Romero JR, Talbot HK, Lee GM, Bell BP, Dooling K. The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine - United States, December 2020. MMWR Morb Mortal Wkly Rep. 2020 Dec 18;69(50):1922-1924. doi: 10.15585/mmwr.mm6950e2.
• Background Roncati L, Roncati M. Emergency use authorization (EUA), conditional marketing authorization (CMA), and the precautionary principle at the time of COVID-19 pandemic. J Public Health Policy. 2021 Sep;42(3):518-521. doi: 10.1057/s41271-021-00299-6. Epub 2021 Jul 27. No abstract available.
• Background MacNeil JR, Su JR, Broder KR, Guh AY, Gargano JW, Wallace M, Hadler SC, Scobie HM, Blain AE, Moulia D, Daley MF, McNally VV, Romero JR, Talbot HK, Lee GM, Bell BP, Oliver SE. Updated Recommendations from the Advisory Committee on Immunization Practices for Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine After Reports of Thrombosis with Thrombocytopenia Syndrome Among Vaccine Recipients - United States, April 2021. MMWR Morb Mortal Wkly Rep. 2021 Apr 30;70(17):651-656. doi: 10.15585/mmwr.mm7017e4.
• Background Krause PR, Gruber MF. Emergency Use Authorization of Covid Vaccines - Safety and Efficacy Follow-up Considerations. N Engl J Med. 2020 Nov 5;383(19):e107. doi: 10.1056/NEJMp2031373. Epub 2020 Oct 16. No abstract available.
• Background Almansour I, Macadato NC, Alshammari T. Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2. Pharmaceuticals (Basel). 2021 Jan 6;14(1):39. doi: 10.3390/ph14010039.
• Background Yang B, Jeang J, Yang A, Wu TC, Hung CF. DNA vaccine for cancer immunotherapy. Hum Vaccin Immunother. 2014;10(11):3153-64. doi: 10.4161/21645515.2014.980686.
• Background Liu MA. A Comparison of Plasmid DNA and mRNA as Vaccine Technologies. Vaccines (Basel). 2019 Apr 24;7(2):37. doi: 10.3390/vaccines7020037.
• Background Lee LYY, Izzard L, Hurt AC. A Review of DNA Vaccines Against Influenza. Front Immunol. 2018 Jul 9;9:1568. doi: 10.3389/fimmu.2018.01568. eCollection 2018.
• 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 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, Kraynyak KA, Patel A, Maslow JN, Morrow MP, Sylvester AJ, Knoblock D, Gillespie E, Amante D, Racine T, McMullan T, Jeong M, Roberts CC, Park YK, Boyer J, Broderick KE, Kobinger GP, Bagarazzi M, Weiner DB, Sardesai NY, White SM. Intradermal SynCon(R) Ebola GP DNA Vaccine Is Temperature Stable and Safely Demonstrates Cellular and Humoral Immunogenicity Advantages in Healthy Volunteers. J Infect Dis. 2019 Jul 2;220(3):400-410. doi: 10.1093/infdis/jiz132.
• Background Muthumani K, Falzarano D, Reuschel EL, Tingey C, Flingai S, Villarreal DO, Wise M, Patel A, Izmirly A, Aljuaid A, Seliga AM, Soule G, Morrow M, Kraynyak KA, Khan AS, Scott DP, Feldmann F, LaCasse R, Meade-White K, Okumura A, Ugen KE, Sardesai NY, Kim JJ, Kobinger G, Feldmann H, Weiner DB. A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates. Sci Transl Med. 2015 Aug 19;7(301):301ra132. doi: 10.1126/scitranslmed.aac7462.

Drugs

Indications