Efficacy and Safety of the RBD-Dimer-Based Covid-19 Vaccine ZF2001 in Adults.

Abstract

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.).

• Authors: Lianpan Dai, Lidong Gao, Lifeng Tao, Sri R Hadinegoro, Musabaev Erkin, Zhifang Ying, Peng He, Rodman T Girsang, Hugo Vergara, Javed Akram, Hindra I Satari, Tanwir Khaliq, Ume Sughra, Ana P Celi, Fangjun Li, Yan Li, Zhiwei Jiang, Dilbar Dalimova, Jaloliddin Tuychiev, Shahlo Turdikulova, Aamer Ikram, Nancy Flores Lastra, Fan Ding, Mahendra Suhardono, Eddy Fadlyana, Jinghua Yan, Zhongyu Hu, Changgui Li, Ibrokhim Y Abdurakhmonov, George F Gao, ZF2001 Global Trial Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 386 Issue 22 Pg. 2097-2111 (06 02 2022) ISSN: 1533-4406 [Electronic] United States
• PMID: 35507481 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2022 Massachusetts Medical Society.

Chemical References

• COVID-19 Vaccines
• Vaccines
• Vaccines, Subunit
• ZF2001 COVID-19 vaccine

Topics

• Adolescent
• Adult
• COVID-19 (prevention & control)
• COVID-19 Vaccines (adverse effects, therapeutic use)
• Double-Blind Method
• Humans
• SARS-CoV-2
• Vaccination
• Vaccines
• Vaccines, Subunit (adverse effects, therapeutic use)
• Young Adult