Successful Phase 3 Trial of Novel COVID-19 Vaccine from Chinese Company

New vaccine for COVID-19 employing receptor-binding domain-dimer-based platform achieves 87.6% efficacy against severe to critical illness.

A novel vaccine against COVID-19, ZF2001 (Zifivax), from the China-based developer, Zhifei, that builds its protein subunit platform with a receptor-binding domain (RBD)-dimer demonstrated safety and efficacy in a phase 3 trial reported in the New England Journal of Medicine.

The double-blind, placebo-controlled trial evaluated a 3-dose regimen of the adjuvanted vaccine administered at 30-day intervals to over 28,000 adult participants at 31 centers in 4 countries. Over 25,000 received all 3 doses, and were followed for approximately 6 months after the final dose.

Lead author Lianpan Dai, PhD, CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China, and colleagues reported an overall efficacy of 75.7% in preventing COVID-19; with 87.6% (95% CI, 70.6 to 95.7) efficacy against severe to critical illness and 86.5% (CI 38.9 to 98.5%) against mortality.

The trial was conducted between December 12, 2020 and December 15, 2021 in regions where the delta variant was initially prevalent, but with alpha and kappa variants also encountered. The investigators reported that efficacy against alpha was 92.7% in short-term follow-up and 88.3% in long-term; 81.4% and 76.1%, respectively against delta; and 84.8% and 75.2%, respectively for the kappa variant.There were comparable adverse events reported in active and placebo groups, with most (98.5%) of grade 1 or 2, and there were no vaccine-related deaths (determined within 7 days of final dose)..

"The high cross-protection conferred by ZF2001 against different SARS-CoV-2 variants is encouraging," Dai and colleagues commented.

Covifenz Vaccine
A separate multinational phase 3 trial in same issue of the Journal demonstrated efficacy and safety of another adjuvanted vaccine with a novel platform, CoVLP+AS03, Covifenz, from Medicago, which employs a plant-based coronavirus-like particle (CoVLP), previously reported here. Those simultaneously published reports also coincide with the currently anticipated FDA approval of the protein-based vaccine from Novavax, which delivers copies of the coronavirus spike protein grown in insect cells.

These developments prompt the question posed in the title of an editorial in this issue of the Journal, "Does the World Still Need New COVID-19 Vaccines?"

Hanna Nohynek, MD, PhD, Finnish Institute for Health and Welfare, Helsinki, Finland, and Annelies Wilder-Smith, MD, PhD, Institute of Preventive and Social Medicine, University of Bern, Switzerland, answer in the affirmative, while acknowledging more than 300 vaccine candidates comprising at least 5 different technology platforms currently in development.

"Many reasons dictate a need for the development of a range of COVID-19 vaccines available for use across the world with the aim of bringing the pandemic under control," Nohynek and Wilder-Smith assert.

They point out that efficacy and safety are not the sole outcomes that are assessed in a country's decision to procure and provide a particular vaccine product. Ease of schedules, effectiveness in routine programs, frequency of needed boosters, costs, cold-chain logistic requirements, manufacturing scalability are among other factors that are considered.

Dai and colleagues point to several other RBD-based COVID-19 vaccines under development, with some having been approved and some in late stage clinical trials. Noting that inactivated virion and full length spike are the 2 other major antigen targets in currently approved vaccines, they indicate that their trial results with this RBD-based product "add a piece to the puzzle in understanding one of the major viral targets used in COVID-19 vaccines."

Nohynek and Wilder-Smith's view suggests that multiple pieces will have to be placed to complete that puzzle. "The next generation of COVID-19 vaccines will need to have broader epitope coverage to provide cross-immunity against SARS-CoV-2 variants, confer a longer duration of protection, and be easy to update in a timely manner for protection against new variants," they opine.

"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—eg, those with underlying immune-compromising or other medical conditions—and pregnant women," say Nohyynek and Wilder-Smith.