ZF2001 was first approved for use in Uzbekistan and later China.[8][9] Production capacity is expected to be one billion doses a year in China[10] and 200 million in Uzbekistan.[11] By July, 100 million doses had been administered in China and Uzbekistan.[12]
Medical uses
It is administered in three doses over a period of two months.[10]
Efficacy
In August 2021, preliminary data from a phase III study with 28,500 participants indicated an overall efficacy of 82% against disease of any severity. Efficacy was 93% against the Alpha variant and 78% against the Delta variant.[13][14]
In July 2021, lab studies showed ZF2001 retained neutralizing effects against B.1.429 (Epsilon), B.1.351(Beta), P.1(Gamma), B.1.525(Eta), B.1.617.1(Kappa), the neutralizing titers decreased ranging from 1.1 fold to 2.1 fold, but the neutralizing efficacy were still good.[15]
Manufacturing
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.[10] Subunit vaccines are delivered alongside adjuvants and booster doses may be required.[16]
The company's vaccine manufacturing facility was put into use in September.[17] In February 2021, management said the company had an annual production capacity of 1 billion doses.[10]
In July 2021, an agreement was reached to produce the vaccine in Uzbekistan starting with 10 million doses a month and eventually 200 million doses a year.[11]
History
Clinical trials
Phase I and II trials and results
In June 2020, 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.[18]
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.[19] In August, an additional Phase II trial was launched with 50 participants aged 60 and above.[20][2]
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.[21]
Phase III trials
In December 2020, 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.[22][17]
In December 2020, 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.[5]
In December 2020, Uzbekistan began a year-long Phase III trial of ZF2001 with 5,000 volunteers between 18 and 59.[23][24]
In December 2020, Ecuador's Minister of Health, Juan Carlos Zevallos announced Phase III trials would involve between 5,000 and 8,000 volunteers.[25]
In February 2021, 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.[26]
In July 2021, Longcom began a randomized, blinded, placebo-controlled phase I with 75 participants aged 3–17.[27][28]
In November 2021, Longcom began a phase II with 400 participants aged 3–17.[29]
Authorizations
Graphs are unavailable due to technical issues. Updates on reimplementing the Graph extension, which will be known as the Chart extension, can be found on Phabricator and on MediaWiki.org.
On 1 March 2021, Uzbekistan granted approval for ZF2001 (under tradename ZF-UZ-VAC 2001) after having taken part in the Phase III trials.[9] In March, Uzbekistan received 1 million doses and started vaccinations in April.[30] By June, a total of 6.5 million doses had been delivered.[31]
In March 2021, China approved of ZF2001 for emergency use after being approved by Uzbekistan earlier in the month.[8]
In June 2021, Malaysia's MyEG signed a letter of intent to purchase 10 million doses of the vaccine.[32]
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.[35]
Rather than injecting a whole virus, subunit vaccines contains virus particles specially selected to stimulate an immune response. Because the fragments cannot cause disease, subunit vaccines are considered very safe.[16] 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.[36]
^Clinical trial number NCT04445194 for "Phase I Clinical Study of Recombinant Novel Coronavirus Vaccine" at ClinicalTrials.gov
^Clinical trial number NCT04466085 for "A Randomized, Blinded, Placebo-controlled Trial to Evaluate the Immunogenicity and Safety of a Recombinant New Coronavirus Vaccine (CHO Cell) With Different Doses and Different Immunization Procedures in Healthy People Aged 18 to 59 Years" at ClinicalTrials.gov
^Clinical trial number NCT04550351 for "A Randomized, Double-blind, Placebo-controlled Phase I Clinical Trial to Evaluate the Safety and Tolerability of Recombinant New Coronavirus Vaccines (CHO Cells) in Healthy People Aged 60 Years and Above" at ClinicalTrials.gov
^Clinical trial number NCT04646590 for "A Phase III Randomized, Double-blind, Placebo-controlled Clinical Trial in 18 Years of Age and Above to Determine the Safety and Efficacy of ZF2001, a Recombinant Novel Coronavirus Vaccine (CHO Cell) for Prevention of COVID-19" at ClinicalTrials.gov
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