The safety and efficacy profile of the COVID-19 vaccine SCB-2019 has been reported in this study.

• In this ongoing phase 2 and 3 double-blind, placebo-controlled trial, adults aged 18 years and older who were in good health or with a stable chronic health condition were included and randomly assigned 1:1 to receive two 0·5 mL intramuscular doses of SCB-2019 (30 μg, adjuvanted with 1·50 mg CpG-1018 and 0·75 mg alum) or placebo (0·9% sodium chloride for injection supplied in 10 mL ampoules) 21 days apart.

• From March 24, 2021, until the cutoff date of Aug 10, 2021, enrollment of 30,174 participants was done; 30,128 of these received their first assigned vaccine (n = 15,064) or a placebo injection (n = 15,064).

• A total of 12,355 baseline SARS-CoV-2-naive participants (6251 vaccines and 6104 placebo recipients) comprised the per-protocol population.

• COVID-19 was diagnosed in 207 after the second dose at 14 days, 52 vaccines vs 155 placebo recipients.

• The overall vaccine efficacy was 67·2% against any COVID-19 severity, 83·7% against moderate-to-severe COVID-19, and 100% against severe COVID-19.

• Overall, participants receiving two doses of SCB-2019 vaccine plus CpG and alum showed development of notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 viruses, including the predominating delta variant.

• There emerged no safety issues in the follow-up period for the efficacy analysis (median of 82 days).