Safety, Tolerability, and Immunogenicity of PIKA-Adjuvanted Re-combinant SARS-CoV-2 Spike (S) Protein Subunit Vaccine in Healthy Adults: Interim results of an open-label and randomised Phase 1 clinical trial.

BackgroundThis COVID-19 pandemic has caused unprecedented morbidity, mortality, and global economic instability. Several approved vaccines demonstrated to be effective prevention against COVID-19. We aimed to evaluate the safety and immunogenicity of the PIKA-adjuvanted recombinant SARS-C0V-2 Spike (S) protein subunit vaccine in adults as a primary immunization and as a booster dose against SARS-C0V-2 infection. MethodsThis was a Phase I, open label, dose-escalation study of 3 dose levels of the SARS-CoV-2 spike antigen administered intramuscularly in combination with a fixed dosage of PIKA adjuvant vaccine to evaluate the safety, tolerability, and immunogenicity of PIKA COVID-19 vaccine candidate in healthy adults. The study planned to have 3 arms: Arm A included subjects who had never received any Covid 19 vaccination or have had Covid 19 infection for > 6 months prior to enrolment, Arm B1 included subjects who had completed their primary series of Covid 19 vaccination with an inactivated Covid 19 vaccine and Arm B2 which included subjects whose primary series was completed with mRNA Covid 19 vaccine. The primary safety outcome was adverse events and safety laboratory parameters, and the secondary immunogenicity outcome was neutralizing antibody geometric mean titers and seroconversion rates against the wild type virus, Delta and Omicron variants. This trial is registered with ClinicalTrials.gov, number NCT05305300. FindingsThis interim analysis report presented the results of Arm A and Arm B1 who completed Day 35 for 2 doses in Arm A and Day 28 for a single booster dose in Arm B1. Safety resultsArm A: 60% of participants reported mainly solicited AEs after first and second vaccine. Most of those were local (mainly pain/tenderness) with few systemic (mainly fever and headaches). The majority of participants reported unsolicited events after vaccine which were mainly investigations in hematology/hepatobiliary/Renal or Urine tract infection urine analysis. At least 80% of the participants reported mild AEs. There were 4 SAEs that were mild and were resolved. Also there were 2 medically attended AEs. Arm B1: Less than 50% of the participants reported solicited adverse events which were mainly local (pain and tenderness) and were mild. Also, less than half of the participants reported unsolicited events which were mainly inves-tigations in hematology/hepatobiliary/Renal or Urine tract infection urine analysis. There were no SAE and Medically attended AEs reported. Immunogenicity resultsArm A: The neutralizing antibody GMTs at day 35 were substantially higher than those at baseline for all dose groups and all variants. Seroconversion rates at 35 days ranged between 85.7% and 92.9% for 5g dose group, 92.9% and 100% for the 10g dose group and between 70% and 80% for the high dose group. Arm B1: Similar to Arm A, neutralizing antibody GMTs at day 28 were substantially higher than those at baseline for all dose groups and all variants. Seroconversion rates at 28 days ranged between 92.9% and 100% for 5g dose group, 80% and 100% for the 10g dose group and between 50% and 64.3% for the high dose group. ConclusionThe findings demonstrated that the PIKA Covid 19 vaccine is safe, well tolerated, immunogenic and can be used as a primary vaccination or as a booster dose in participants who had completed an inactivated Covid 19 vaccination series. A comparison of the immune responses presented in this interim analysis showed that geometric mean titer (GMTs) of neutralizing antibody against wild type of SARS-CoV-2 virus, Delta and Omicron of the 5g group was higher than the 10 g and 20 g, therefore the 5g was selected as the recommended dose for the Phase II and III clinical development of the PIKA Covid 19 vaccine.