A phase 1, single-center, randomized, dose finding study to evaluate the safety, tolerability, and immunogenicity of a prophylactic COVID-19 pDNA vaccine after single ascending doses in healthy adults

Background: SARS-CoV-2 has been responsible for a worldwide public health crisis and a pandemic that began in February 2020, with approximately 679 million cases and over 6.7 million deaths to date. Despite the existence of approved COVID-19 vaccines, these vaccines are either based on mRNA technology or viral vectors. Imam Abdulrahman Bin Faisal University (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. The pDNA vaccine developed by IAU encodes the full-length, optimized version of the SARS-CoV-2 Spike protein. Key advantages of this pDNA vaccine are that it is cost-effective, thermally stable, and can be used to administer multiple immunizations without incurring anti-vector responses, making it a promising candidate as a vaccine booster dose. Methods: This study aims to investigate the safety, tolerability, and immunogenicity of this prophylactic pDNA vaccine as a booster vaccine to protect against COVID-19 when administered as an intramuscular injection in a single ascending dose design. In total, 42 eligible healthy subjects will be enrolled in the study. The subjects will be randomized to receive either the investigational vaccine or placebo (Saline) at a 3:1 allocation ratio. Participants will have received two doses of a SARS-CoV-2 mRNA vaccine at least 4 months prior to enrollment. Subjects will be enrolled in a dose-escalating study and assigned to one of the three cohorts (Cohort 1: low-dose; Cohort 2: mid-dose; Cohort 3: high-dose). Primary endpoints will include local reactions and systemic reactions for up to 7 days following vaccination, adverse events from vaccination to 1 month, and serious adverse events from vaccination to 6 months. Secondary endpoints will include the evaluation of binding antibody (bAB) and neutralizing antibody (nAB) responses at vaccination day (Visits 1) and 30 days after vaccination (Visit 4), the ratio of bAB to nAB titers at Visits 1 and 4, and cellular immune responses (CD3, CD4, CD8, CD45RA, CCR7, IFN-γ, IL-2, IL-4, IL-13, and TNF) at Visits 1 and 4. Discussion: The study will be critical to determine the safety and immunogenicity of the pDNA vaccine in participants who have previously received a COVID-19 mRNA vaccine. This study will also aim to determine the safest maximum tolerated dose in participants receiving the pDNA vaccine. Trial registration: ClinicalTrials.gov SCTR No 23010802.