A plant-based vaccine developed in Canada and a protein subunit vaccine from China proved safe and effective against symptomatic COVID-19, a pair of phase III trials found.
The two-dose plant-based vaccine, a combination of coronavirus-like particles in plants plus an adjuvant, showed 69.5% efficacy (95% CI 56.7-78.8) against any symptomatic disease caused by five pre-Omicron variants, reported Brian Ward, MD, of developer Medicago in Quebec, and colleagues in the CoVLP Study Team.
A post-hoc analysis found that the vaccine (CoVLP+AS03) had 78.8% (95% CI 62.1-82.5) efficacy against moderate-to-severe disease, with no severe cases in the vaccine group, they wrote in the New England Journal of Medicine (NEJM).
A second NEJM study also showed positive results for a vaccine (ZF2001) out of China against symptomatic and severe-to-critical COVID-19 for at least 6 months after full vaccination.
But in an accompanying editorial, experts raised the question: “Does the world still need new COVID-19 vaccines?”
“Both of these COVID-19 vaccines are produced on new technology platforms,” wrote Hanna Nohynek, MD, PhD, of the University of Bern in Switzerland, and Annelies Wilder-Smith, MD, PhD, of the World Health Organization (WHO), in the editorial. “Both vaccines have the advantage of not requiring extreme coldchain procedures for storage, which makes them user-friendly in primary health care settings as well as in low- and middle-income countries.”
Nohynek and Wilder-Smith pointed out that both trials included “mostly working age adults,” so no vaccine efficacy data was available for older adults, and both lacked efficacy data against Omicron, “as well data on durability of protection and safety in subpopulations such as older persons, pregnant women, and persons with immunosuppression.”
Still, they heralded the use of new vaccine platforms as new weapons to be deployed in the fight against COVID.
“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 subpopulations,” Nohynek and Wilder-Smith said, adding that the world is still in need of a vaccine that prevents infection.
“To slow down the circulation of the virus and to limit the speed at which further variants emerge, new vaccines that have a substantial effect on reducing mild infection and transmission are needed,” they wrote.
CoVLP+AS03 is currently approved for use in Canada, while ZF2001 is approved for use in China and several other countries. As of press time, there was no word on whether the developers of ZF2001 plan to submit data to FDA for approval. Medicago’s CEO recently said the company has started the filing process for FDA approval.
“In the cells of the plant leaves, the expression of the SARS-CoV-2 S protein leads to the formation of virus-like particles,” Ward’s group wrote, adding that they then harvest and purify these particles, which are stable for 6 months. The adjuvant system has been used in pandemic influenza vaccines and “initiates a transient innate response and increases the magnitude, quality, and durability of adaptive responses.”
The phase III trial was conducted from March 15 to Sept. 2, 2021 in the U.S., Canada, Mexico, Brazil, Argentina, and the U.K. Participants were adults with no prior history of COVID vaccination or COVID infection. They were randomized to receive either two injections of CoVLP+AS03 vaccine or placebo, 21 days apart.
Overall, 24,141 participants were randomized and included in the intention-to-treat (ITT) population. Median age was 29, 51% were men, and about 15% were seropositive at baseline. Nearly all were younger than age 65 (90%) and white (89%), with 82% reporting Hispanic/Latinx ethnicity. Participants with pre-existing conditions were underenrolled, due to surges of Delta and Gamma variants that made participating in a clinical trial more risky, the authors noted.
The primary vaccine efficacy endpoint included 165 cases in the ITT population, with 40 in the vaccine group and 125 in the placebo group. Vaccine efficacy was 78.7% (95% CI 30.2-95.1) in the small group with pre-existing conditions.
There were three severe cases that led to two hospitalizations in the placebo group, the authors noted. A post-hoc analysis found vaccine efficacy was higher (86.0%, 95% CI 66.2-95.1) against moderate-to-severe disease among those who were seronegative at baseline. There were no deaths related to COVID-19.
The most common systemic adverse events (AEs) were headache, myalgia, fatigue, and “a feeling of general discomfort.” Grade 2 and 3 AEs occurred more frequently after the second dose. Three participants reported grade 4 AEs, two in the vaccine group (headache, chills, and fever) and one in the placebo group (headache).
The phase III trial of a three-dose protein subunit vaccine, featuring a “dimeric form” of the SARS-CoV-2 receptor-binding domain (RBD) with an adjuvant. It showed vaccine efficacy of 75.7% (95% CI 71.0-79.8) against symptomatic COVID and 87.6% (95% CI 38.9-98.5) efficacy against severe disease.
“Although the receptor-binding domain (RBD) has been widely used as the COVID-19 vaccine target … data regarding the efficacy of RBD-based vaccines are lacking,” wrote George Gao, PhD, of the Chinese Academy of Sciences in Beijing, and colleagues in the ZF2011 Global Trial Group.
The study was conducted from Dec. 12, 2020 to Dec. 15, 2021 in Uzbekistan, Indonesia, Pakistan, and Ecuador. Adults received either three injections of vaccine or placebo, 30 days apart.
Overall, there were 25,193 participants in the updated analysis. Median age was 37, about 68% were men, and 78% were “Asian, but not Ethnic Chinese.”
There were a total of 158 cases in the vaccine group and 580 in the placebo group. Six participants in the vaccine group and 43 in the placebo group had severe-to-critical COVID. There were two deaths in the vaccine group and 12 in the placebo group, for vaccine efficacy of 86.5% (95% CI 38.9-98.5) against death.
AEs were mostly mild or moderate, with the authors noting 98.5% were grade 1 or 2. Four participants had treatment-related serious AEs (hypersensitivity), which resolved after treatment “without sequelae.” There were 48 deaths over 6 months of follow-up, but none were attributable to the vaccine, they added.
Ward and co-authors disclosed support from Medicago and the Canadian government. Some co-authors are Medicago employees.
Ward disclosed support from Novartis. Co-authors disclosed multiple relationships with industry including GlaxoSmithKline.
Gao and colleagues disclosed support from Anhui Zhifei Longcom Biopharmaceutical and the Chinese government. Some co-authors are Zhifei Longcom Biopharmaceutical employees.
A co-author disclosed support from the Bill & Melinda Gates Foundation. Gao and several co-authors disclosed being co-inventors on a patent for the RBD dimer antigen used in this vaccine.
Nohynek disclosed being a government employee and receiving European Commission funding. Wilder-Smith disclosed no relationships with industry.