Two studies based on phase 3 clinical trials published yesterday in the New England Journal of Medicine show promising results for two novel COVID-19 vaccine platforms—a plant-based coronavirus-like particle vaccine, and a receptor-binding domain (RBD)–dimer-based vaccine.
And neither vaccine requires extreme cold chain storage, which makes them appealing candidates for low- and middle-income countries, a key component of global COVID-19 vaccination efforts.
Vaccines perform well despite variants
The first vaccine is a plant-based particle vaccine, developed by Medicago/GSK, and was tested on participants in Argentina, Brazil, Canada, Mexico, the United Kingdom, and the United States from Mar 15 to Sep 2, 2021.
The vaccine, CoVLP, was administered in two shots 21 days apart, and results were compared to placebo. The study continued until at least 160 COVID-19 cases were detected in participants at least 7 days following the second dose of vaccine.
A total of 24,141 volunteers participated in the trial. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7% to 78.8%) against any symptomatic COVID-19 caused by five variants that were identified by sequencing, the authors found. Results were even stronger for efficacy against moderate-to-severe disease, at 78.8% (95% CI, 55.8% to 90.8%).
No severe cases or deaths were recorded in the vaccine group. The vaccine group had more adverse effects, but none were severe.
"CoVLP+AS03, like all currently deployed vaccines, was designed to target the original viral strain, but no case caused by this strain was identified," the authors said. "The context in which vaccines are currently being tested has clearly changed since early in the pandemic."
The authors said the performance of CoVLP is similar to current vaccines in use against current strains.
Three-dose vaccine 88% effective against severe COVID
The second vaccine, ZF2001, was tested at 31 clinic sites in Uzbekistan, Indonesia, Pakistan, and Ecuador, and later in China. The vaccine is made by Anhui Zhifei Longcom of China.
Participants were randomized to receive placebo or three injections of vaccine administered 30 days apart. The trial took place from Dec 12, 2020, to Dec 15, 2021.
Only 158 of 12,625 participants in the ZF2001 group contracted COVID-19 during the trial, compared with 580 of 12,568 participants in the placebo group. Vaccine efficacy against infection was 75.7% (95% CI, 71.0% to 79.8%) and 87.6% (95% CI, 70.6% to 95.7%) against severe to critical disease.
Two participants in the vaccine group, and 12 in the placebo group, died of COVID-19, resulting in an 86.5% (95% CI, 38.9% to 98.5%) efficacy rate against death.
Genotype sampling from COVID-19 cases in the study showed primarily Delta, Alpha, and B.1.617.3 variants. The authors said vaccine efficacy was 76.1% (95% CI, 70.0% to 81.2%) against Delta, 88.3% (95% CI, 66.8% to 97.0%) against Alpha, and 75.2% (95% CI, 55.3% to 87.0%) against Kappa.
"The high cross-protection conferred by ZF2001 (an antigen based on the Wuhan-Hu-1 sequence) against different SARS-CoV-2 variants is encouraging," the authors wrote.
Multiple vaccine platforms needed
Neither trial assessed how well the vaccines performed against asymptomatic infections, and both had very few participants over the age of 60. But in an editorial, Hanna Nohynek, MD, PhD, and Annelies Wilder-Smith, MD, PhD, write that the results seen in these trials are encouraging.
Currently 31 COVID-19 vaccines are already in large-scale use after conditional approval by national regulatory authorities or under the World Health Organization Emergency Use Listing, and more than 300 are in development.
Moreover, unlike this time last year, global vaccine supply is now meeting demand. Still, the emergence of variants that can evade vaccine protection supports a broad range of COVID-19 vaccine platforms, the authors argue. Mix-and-match strategies may prove to be useful in future booster campaigns. And vaccines that don't require specialized cold-chain storage may prove useful in limited-resource settings.
"We should remain agile in fine-tuning the best use of Covid-19 vaccines for the greatest effect on global public health by acknowledging trade-offs," they write.
"With more vaccine platforms available, we can possibly improve decision making regarding the selection of a vaccine, since different vaccine platforms may be more suitable for certain age groups, certain subpopulations (e.g., those with underlying immune-compromising or other medical conditions), and pregnant women."