ZF2001

ZF2001, trade-named RBD-Dimer, is an adjuvanted protein subunit COVID-19 vaccine developed by Anhui Zhifei Longcom in collaboration with the Institute of Microbiology at the Chinese Academy of Sciences. As of December 2020, the vaccine candidate was in Phase III trials with 29,000 participants in China, Ecuador, Malaysia, Pakistan, and Uzbekistan.
ZF2001 employs technology similar to other protein-based vaccines in Phase III trials from Novavax, Vector Institute, and Medicago. It is administered in 3 doses over a period of 2 months.
ZF2001 was first approved for use in Uzbekistan and later China. Production capacity is expected to be one billion doses a year. Phase II results published in "The Lancet" on the three dose administration showed seroconversion rates of neutralizing antibodies of between 92% to 97%.
Description.
As described in Cell, the CoV spike receptor-binding domain (RBD) is an attractive vaccine target for coronaviruses but is constrained by limited immunogenicity, however a dimeric form of MERS-CoV RBD offers greater protection. The RBD-dimer significantly increases neutralizing antibodies compared to a conventional monomeric form and protected mice against MERS-CoV infection. CoV RBD-dimer have been produced at high yields in pilot scale production.
Rather than injecting a whole virus, subunit vaccines contains virus particles specially selected to stimulate an immune response. Because the fragments are incapable of causing disease, subunit vaccines are considered very safe. Subunit vaccines in widespread use include the Hepatitis B vaccine and Pertussis vaccine. However, as only a few viral components are included in the vaccine which does not display the full complexity of the virus, their efficacy may be limited. Subunit vaccines are delivered alongside adjuvants and booster doses may be required.
According to industry experts, production for this kind of vaccine is stable and reliable, and easier to achieve large-scale industrial production at home and overseas. However it was noted it can be very inconvenient for people to come back for a second and third dose.
Development.
Phase I and II trials and results.
In June, Longcom began a double-blind, randomized, placebo parallel controlled Phase I trial with 50 participants aged 18–59 in Chongqing divided into low-dose, high-dose, and placebo groups.
In July, Longcom began a randomized, double-blind, placebo-controlled Phase II trial with 900 participants aged 18–59 in Changsha, Hunan divided into low-dose, high-dose, and placebo groups. In August, an additional Phase II trial was launched with 50 participants aged 60 and above.
In Phase II results published in "The Lancet," on the two-dose schedule, seroconversion rates of neutralizing antibodies after the second dose were 76% (114 of 150 participants) in a 25 μg group and 72% (108 of 150) in a 50 μg group. On the three-dose schedule, seroconversion rate of neutralizing antibodies after the third dose were 97% (143 of 148 participants) in the 25 μg group and 93% (138 of 148) in the 50 μg group. 7 to 14 days after the administration of the third dose, the GMTs of neutralizing antibodies reached levels that were significantly higher than observed in human convalescent serum of recovering COVID-19 patients, especially in the 25 μg group.
Phase III trials.
In December, Longcom began enrollment of a Phase III randomized, double-blind, placebo-controlled clinical trial for 29,000 participants, including 750 participants between 18-59 and 250 participants 60 and older in China and 21,000 participants between 18-59 and 7,000 participants 60 and older outside China.
In December, Malaysia's MyEG announced it would conduct Phase III trials. If the trials were successful, MyEG would be the sole distributor of ZF2001 in Malaysia for 3 years.
In December, Uzbekistan began a year-long Phase III trial of ZF2001 with 5,000 volunteers between 18 and 59.
In December, Ecuador's Minister of Health, Juan Carlos Zevallos announced Phase III trials would involve between 5,000 and 8,000 volunteers.
In February, Pakistan's Drug Regulatory Authority (DRAP) approved Phase III trials with approximately 10,000 participants to be conducted at UHS Lahore, National Defense Hospital, and Agha Khan Hospital.
Discussions to begin Phase III trials are also underway in Indonesia.
COVID-19 Variants.
In February, lab studies of twelve serum samples taken from recipients of BBIBP-CorV and ZF2001 retained neutralizing activity against 501.V2 variant although with weaker activity than against the original virus. For ZF-2001, geometric mean titers declined by 1.6-fold, from 106.1 to 66.6, which was less than antisera from mRNA vaccine recipients with a 6-folds decrease. Preliminary clinical data from Novavax and Johnson & Johnson also showed they were less effective in preventing COVID-19 in South Africa, where the new variant is widespread.
Manufacturing.
The company's vaccine manufacturing facility was put into use in September. In February 2021, Pu Jiang, General Manager of Zhifei Longcom, said the company had an annual production capacity of 1 billion doses.
Marketing and deployment.
On March 1, Uzbekistan granted approval for ZF2001 (under tradename ZF-UZ-VAC 2001) after having taken part in the Phase III trials. In March, Uzbekistan received 1 million doses and started vaccinations in April. By May, a total of 3 million doses had been delivered.
On March 15, China approve of ZF2001 for emergency use after being approved by Uzbekistan earlier in the month.