Safety and immunogenicity of an inactivated virus particle vaccine for SARS-CoV-2, BIV1-CovIran: findings from double-blind, randomised, placebo-controlled, phase I and II clinical trials among healthy adults

OBJECTIVE: Assessing safety and immunogenicity of an inactivated whole virus particle vaccine. DESIGN: Single-centre, double-blind, randomised, placebo-controlled, phase I (stage I: 18–50, stage II: 51–75 years), phase II (18–75 years) clinical trials. SETTING: 29 December 2020 to 22 April 2021. PARTICIPANTS: Stage I-phase I: 56 participants; stage II-phase I: 32; phase II: 280. INTERVENTION: During stage I, participants randomly (3:3:1) received 3 µg, 5 µg vaccine or placebo in a 14-day interval. Participants in stage II received two shots of 5 µg vaccine or placebo (3:1). In phase II, participants received 5 µg vaccine or placebo (4:1) in a 28-day interval. PRIMARY AND SECONDARY OUTCOME MEASURES: Safety assessment and immunogenicity assessment via antibody response and conventional virus neutralisation test (cVNT). RESULTS: All adverse events (AEs) were mild or moderate and transient in both phase I and phase II, and no AEs of special interest were reported. The seroconversion-rate of neutralising, antireceptor binding-domain (RBD) and anti-spike-glycoprotein (anti-S) antibodies 14-days after second dose of 5 µg vaccine in stage I was 70.8% (95% CI 48.9% to 87.4%), 87.5% (95% CI 67.6% to 97.3%), 91.7% (95% CI 73.0% to 99.0%). The antibody titres increased more among 5 µg than 3 µg. The corresponding rates for 3 µg vaccine were 45.8% (95% CI 25.6% to 67.2%), 54.2% (95% CI 32.8% to 74.5%) and 70.8% (95% CI 48.9% to 87.4%), respectively. In stage II, 100% (95% CI 84.6% to 100%), 86.4% (95% CI 65.1% to 97.1%) and 86.4% (95% CI 65.1% to 97.1%) of participants seroconverted for neutralising, anti-RBD and anti-S antibodies. In phase II, the seroconversion rate of neutralising-antibody was 82.8% (95% CI 77.0% to 87.6%), anti-RBD 77.0% (95% CI 70.7% to 82.6%) and anti-S 79.9% (95% CI 73.8% to 85.1%) on day 42. In the cVNT, the sera at 1/64 times dilution would neutralise SARS-CoV-2 among 91.7%, 77.3% and 82.5% of vaccinated participants in phase I-stage I, phase I-stage II and phase II clinical trials, respectively. CONCLUSIONS: These results support further evaluation of this inactivated whole virus particle vaccine. TRIAL REGISTRATION NUMBERS: IRCT20201202049567N1 and IRCT20201202049567N2 for phase I and IRCT20201202049567N3 for phase II.