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

Sever Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a newly emerging coronavirus that is known to cause worldwide public health crisis and an ongoing pandemic since February 2020 with 219 million cases and 4.5 million deaths as of September 2021 (1). The World Health Organization (WHO) has given the term Coronavirus Diseases 19 (COVID-19) to indicate the illness caused by SARS-CoV-2. Individuals infected SARS-CoV-2 can have wide ranges of symptoms that varies between mild to very severe (1,2). Despite the existence of several COVID-19 vaccine that are approved under emergency use by EMA and FDA (2,3,4,5,6,7), there is a global demand for the manufacturing of sufficient vaccine to control the COVID-19 worldwide. In addition, there is a demand for the development and deployment of new COVID-19 vaccine that is generic and thermally stable for which the vaccine can be stored for a longer period, especially in countries that lacks the infrastructure capabilities to store the vaccine under freezing temperature. Imam Abdulrahman Bin Faisal University (IAU) has developed an investigational prophylactic COVID-1 pDNA vaccine using a codon optimized spike gene of the SARS-CoV-2 (S.opt.FL). The developed pDNA vaccine possess several advantages; Unlike with mRNA vaccine platforms, pDNA is more stable. Therefore, cold-chain shipment and storage is not needed. Also, the chance for anti-vector immunity generated after immunization viral vector vaccine platform is omitted in pDNA vaccine platform. Importantly, the pDNA can stimulate humoral and cellular immune responses (9,10,11). IAU COVID-19 vaccine Almansour-001 consists of a plasmid DNA (pDNA) carrying a synthetic, codon-optimized, gene insert that encodes spike (S) gene of COVID-19. The pDNA included in the study is (pVAX-1), an FDA approved plasmid for the application in clinical trials. Preclinical study conducted at Imam Abdulrahman Bin Faisal University (IAU) have demonstrated that S.opt.FL and S1.opt are immunogenic in mice (8). The study investigated 3 doses versus 4 doses of DNA vaccine. The study demonstrated three doses S1.opt.FL elicited high bAB and nAB responses (8) as well as interferon-Gamma as an indicator of cellular immunity. Previous work on pDNA vaccines encoding the S gene of SARS-CoV, MERS-CoV, and SARS-CoV-2 have demonstrated that pDNA vaccine is safe and well tolerated (12,13,14,15). The purpose of this clinical trial is to evaluate the safety and immunogenicity of 2 or 3 dose regimen of investigational pDNA vaccine encoding S.opt.FL gene inserted into pVAX1 plasmid (Almansour-001). Here, in this phase-I study, the pDNA vaccine candidate is administered intramuscularly (IM) by immunizing healthy adults (18-55 years). The S.opt.FL pDNA vaccine is evaluated in dose wise manner in three different cohorts (cohort 1: low dosage of pDNA vaccine "1 mg", cohort 2: middle dosage of pDNA vaccine "2 mg", cohort 3: high dosage of pDNA vaccine "4 mg")