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Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults
Lianpan Dai1, Lidong Gao1, Lifeng Tao1
1From the CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (L.D., Y.L., J.Y., G.F.G.), the National Institute for Food and Drug Control (Z.Y., P.H., Z.H., C.L.), and Beijing Keytech Statistical Technology (Z.J.), Beijing, the Hunan Provincial Center for Disease Control and Prevention, Changsha (L.G., F.L.), and Anhui Zhifei Longcom Biopharmaceutical, Hefei (L.T., F.D.) - all in China; the Child Health Department, Faculty of Medicine, University of Indonesia, and Cipto Mangunkusumo Hospital (S.R.H., H.I.S.), and PT Jakarta Biopharmaceutical Industry (M.S.), Jakarta, and the Child Health Department, Faculty of Medicine, Padjadjaran University, and Hasan Sadikin General Hospital, Bandung (R.T.G., E.F.) - all in Indonesia; the Research Institute of Virology (M.E., J.T.), the Center for Advanced Technologies (D.D., S.T.), and the Center of Genomics and Bioinformatics (I.Y.A.) - all in Tashkent, Uzbekistan; Biodimed Unidad Alemania (H.V.), the Department of Infectiology, Novaclínica Santa Cecilia (A.P.C.), and Biodimed Unidad Eloy Alfaro (N.F.L.) - all in Quito, Ecuador; and University of Health Sciences Lahore, Lahore (J.A.), Shaheed Zulfiqar Ali Bhutto Medical University (T.K.) and the National Institute of Health (A.I.), Islamabad, and Al-Shifa Trust Eye Hospital, Rawalpindi (U.S.) - all in Pakistan.
Background:
The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an adjuvant, was shown to be safe, with an acceptable side-effect profile, and immunogenic in adults in phase 1 and 2 clinical trials.
Methods:
We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to investigate the efficacy and confirm the safety of ZF2001. The trial was performed at 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador; an additional center in China was included in the safety analysis only. Adult participants (≥18 years of age) were randomly assigned in a 1:1 ratio to receive a total of three 25-μg doses (30 days apart) of ZF2001 or placebo. The primary end point was the occurrence of symptomatic coronavirus disease 2019 (Covid-19), as confirmed on polymerase-chain-reaction assay, at least 7 days after receipt of the third dose. A key secondary efficacy end point was the occurrence of severe-to-critical Covid-19 (including Covid-19-related death) at least 7 days after receipt of the third dose.
Results:
Between December 12, 2020, and December 15, 2021, a total of 28,873 participants received at least one dose of ZF2001 or placebo and were included in the safety analysis; 25,193 participants who had completed the three-dose regimen, for whom there were approximately 6 months of follow-up data, were included in the updated primary efficacy analysis that was conducted at the second data cutoff date of December 15, 2021. In the updated analysis, primary end-point cases were reported in 158 of 12,625 participants in the ZF2001 group and in 580 of 12,568 participants in the placebo group, for a vaccine efficacy of 75.7% (95% confidence interval [CI], 71.0 to 79.8). Severe-to-critical Covid-19 occurred in 6 participants in the ZF2001 group and in 43 in the placebo group, for a vaccine efficacy of 87.6% (95% CI, 70.6 to 95.7); Covid-19-related death occurred in 2 and 12 participants, respectively, for a vaccine efficacy of 86.5% (95% CI, 38.9 to 98.5). The incidence of adverse events and serious adverse events was balanced in the two groups, and there were no vaccine-related deaths. Most adverse reactions (98.5%) were of grade 1 or 2.
Conclusions:
In a large cohort of adults, the ZF2001 vaccine was shown to be safe and effective against symptomatic and severe-to-critical Covid-19 for at least 6 months after full vaccination. (Funded by the National Science and Technology Major Project and others; ClinicalTrials.gov number, NCT04646590.).
