Since the beginning of the 2019 coronavirus disease pandemic (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), scientists and politicians have continued to work relentlessly to control the pandemic. The availability of multiple vaccines against COVID-19, developed on different platforms, is considered a powerful tool to limit the pandemic.
Background
Previous studies have reported the effectiveness of vaccines against COVID-19 developed on various platforms, such as messenger RNA (mRNA) and recombinant protein with adjuvant. These vaccines have been shown to be between 90 and 96% effective in preventing severe COVID-19 against the original SARS-CoV-2 strain.
Several new variants of SARS-CoV-2 have emerged due to genomic mutations, which have been categorized as variants of concern (VOCs) and variants of interest (VOIs) based on their tolerability, virulence, and ability to evade immune protection.
The SARS-CoV-2 Delta and Omicron variants are classified as VOCs due to their high transmittance. These variants were predominant in most countries around the world and increased the rate of breakthrough infection. The increased rate of sudden infections indicates a reduced efficacy of available COVID-19 vaccines against new variants of SARS-CoV-2.
The researchers developed a protein-based subunit vaccine against COVID-19, known as ZF2001, which targets the tandem-repeating dimeric receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. They produce the antigenic protein in Chinese hamster ovary cells and treat it with aluminum hydroxide (adjuvant) to develop the vaccine. One of the main advantages of this vaccine is that it does not require strict cold conditions for storage and transport.
Study: Efficacy and safety of the RBD-dimer-based Covid-19 vaccine ZF2001 in adults. Image Credit: LookerStudio / Shutterstock
New research
Preliminary preclinical studies with ZF2001 in rodents and macaques have shown promising efficacy against SARS-CoV-2. In addition, phase 1 and 2 clinical trials have also reported that the vaccine is safe and effective in humans. The researchers developed a three-dose regimen in phase 3 of the ZF2001 trial.
A new study published in the New England Journal of Medicine discusses the efficacy and safety profile of ZF2001 in adults, based on a randomized, placebo-controlled, multinational, double-blind, phase 3 study. During this study, the SARS variant CoV-2 Delta was predominantly circulating worldwide.
This study was conducted in thirty-one clinical centers in Indonesia, Ecuador, Uzbekistan and Pakistan. Another center was set up in China just to determine the safety profile of the ZF2001. In this phase 3 trial, all participants were 18 years of age or older and were inoculated with three doses of 25-μg ZF2001 or placebo at 30-day intervals. The efficacy of the vaccine was evaluated at least seven days after the third dose of vaccine and was followed for six months.
Key findings
The researchers designed the current study as a case-based study. In this study, at least one dose of ZF2001 or placebo was administered to 28,873 participants between 12 December 2020 and 15 December 2021 and was considered for safety analysis. The researchers determined the effectiveness of the vaccine by analyzing 25,193 participants who received three doses of the vaccine.
The researchers reported that severe to critical SARS-CoV-2 infection occurred in six participants who were vaccinated with ZF2001 and forty-three participants who received placebo. The estimated efficacy of the severe COVID-19 vaccine was 92.9% in the short-term follow-up and 87.6% in the long-term follow-up. In addition, two COVID-19-related deaths were reported, among those vaccinated with ZF2001 and twelve participants who received placebo. Importantly, no vaccine-related deaths occurred and most adverse reactions were found to be around grade 1 or 2.
The researchers analyzed both the short-term and long-term efficacy of the vaccine. They reported that the short-term efficacy of three doses of ZF2001 was 81.4% and the long-term efficacy was 75.7%. The authors state that this vaccine not only met the predetermined criteria for success, but significantly exceeded it.
The present study shows that ZF2001 provides a high level of cross-protection against different variants of SARS-CoV-2. The vaccine has been found to be very effective against the Alpha, Kappa and Delta variants. Importantly, this study established the safety and reactogenicity profile of ZF2001, which was found to be comparable to the phase 1 and 2 reports. The authors also state that this phase 3 trial included older participants who are over sixty years of age and show fewer adverse events and reactogenicity compared to younger participants. The findings strongly support the effectiveness of the ZF2001 vaccine against the SARS-CoV-2 virus.
Limits
The authors pointed out some of the limitations associated with the present study. First, the study cohort included predominantly Asian participants, ie. 78.5%; however, the ideal cohort must include a diverse population. In addition, the number of older participants over the age of sixty is limited in the study cohort. Therefore, in the future, the effectiveness of the vaccine must be evaluated for this group in real conditions. The present study does not evaluate the efficacy of the vaccine against asymptomatic COVID-19 infection, which may be considered in future studies.
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