Safety and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older: two single-center, randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials

Abstract

COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9-171.2) and 102.6 (95% CI 75.2-140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination.

Fig. 1. Trial profile.

a In phase 1 trial, 415 volunteers were recruited and screened for eligibility, among which 168 participants were sequentially enrolled and randomly assigned. All participants completed the full doses of vaccination and the planned visits within 28 days after the last dose vaccination. b In phase 2 trial, 1039 volunteers were recruited and screened for eligibility, among which 960 participants were enrolled and randomly assigned. 959 participants received the first dose vaccination, with 1 participant refused to receive vaccination after randomization. 952 participants completed the full doses of vaccination and the planned visits within 30 days after the last dose vaccination

Fig. 2. Specific T-cell response measured by ELISpot in phase 1 trial.

In phase 1 trial, level of IFN-γ was detected by ELISpot before the first dose vaccination, 14 and 28 days after the last dose vaccination (a, b), and then the positive rate of IFN-γ was calculated (c, d). Data are presented as mean and 95% CI. a, c: Adult group. b, d: Elderly group