From 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.
N Engl J Med. 2022 Jun 2;386(22):2097-2111. doi: 10.1056/NEJMoa2202261. Epub 2022 May 4.
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.
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.
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.
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.).
ZF2001 疫苗含有严重急性呼吸综合征冠状病毒 2 的受体结合域二聚体和作为佐剂的氢氧化铝，在 1 期和 2 期临床试验中已显示出在成年人中的安全性、可接受的副作用特征和免疫原性。
我们开展了一项随机、双盲、安慰剂对照、3 期临床试验，以研究 ZF2001 的疗效并确认其安全性。该试验在乌兹别克斯坦、印度尼西亚、巴基斯坦和厄瓜多尔的 31 个临床中心进行；中国的一个额外中心仅被纳入安全性分析。成年参与者（≥18 岁）按 1:1 的比例随机分配，接受总计 3 次 25μg 剂量（间隔 30 天）的 ZF2001 或安慰剂。主要终点是在第 3 次给药后至少 7 天，通过聚合酶链反应检测确诊的有症状的 2019 年冠状病毒病（Covid-19）。一个关键的次要疗效终点是在第 3 次给药后至少 7 天发生严重至危重症的 Covid-19（包括与 Covid-19 相关的死亡）。
在 2020 年 12 月 12 日至 2021 年 12 月 15 日期间，共有 28873 名参与者至少接受了一剂 ZF2001 或安慰剂，并被纳入安全性分析；共有 25193 名完成了 3 剂方案的参与者，他们大约有 6 个月的随访数据，被纳入了 2021 年 12 月 15 日第二个数据截止日期进行的更新主要疗效分析。在更新分析中，在 ZF2001 组的 12625 名参与者中有 158 例和安慰剂组的 12568 名参与者中有 580 例报告了主要终点病例，疫苗有效性为 75.7%（95%置信区间[CI]，71.0 至 79.8）。在 ZF2001 组中有 6 例和安慰剂组中有 43 例发生严重至危重症的 Covid-19，疫苗有效性为 87.6%（95%CI，70.6 至 95.7）；与 Covid-19 相关的死亡分别发生在 2 名和 12 名参与者中，疫苗有效性为 86.5%（95%CI，38.9 至 98.5）。两组中不良反应和严重不良反应的发生率相当，且无疫苗相关死亡。大多数不良反应（98.5%）为 1 级或 2 级。
在一大群成年人中，ZF2001 疫苗在完全接种后至少 6 个月内显示出对有症状和严重至危重症 Covid-19 的安全性和有效性。（由国家科技重大专项和其他机构资助；临床试验.gov 编号，NCT04646590。）
