ZF2001

ZF2001, trade-named Zifivax or ZF-UZ-VAC-2001, 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.[1][2] The vaccine candidate is in Phase III trials with 29,000 participants in China, Ecuador, Malaysia, Pakistan, and Uzbekistan.[3][4]

ZF2001
Vaccine description
TargetSARS-CoV-2
Vaccine typeProtein subunit
Clinical data
Trade namesZifivax
Routes of
administration		Intramuscular
ATC code
  • None
Legal status
Legal status
Identifiers
DrugBank
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ZF2001 employs technology similar to other protein-based vaccines[5] in Phase III trials from Novavax, Vector Institute, and Medicago.[6]

ZF2001 was first approved for use in Uzbekistan and later China.[7][8] Production capacity is expected to be one billion doses a year in China[9] and 200 million in Uzbekistan.[10] By July, 100 million doses had been administered in China and Uzbekistan.[11]

Medical uses

It is administered in three doses over a period of two months.[9]

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.[12][13]

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.[14]

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.[9] Subunit vaccines are delivered alongside adjuvants and booster doses may be required.[15]

The company's vaccine manufacturing facility was put into use in September.[16] In February 2021, management said the company had an annual production capacity of 1 billion doses.[9]

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.[10]

History

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.[17]

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.[18] In August, an additional Phase II trial was launched with 50 participants aged 60 and above.[19][1]

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.[20]

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.[21][16]

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.[4]

In December 2020, Uzbekistan began a year-long Phase III trial of ZF2001 with 5,000 volunteers between 18 and 59.[22][23]

In December 2020, Ecuador's Minister of Health, Juan Carlos Zevallos announced Phase III trials would involve between 5,000 and 8,000 volunteers.[24]

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.[25]

The vaccine is also being trialed in Indonesia.[13]

Children and adolescents trial

In July 2021, Longcom began a randomized, blinded, placebo-controlled phase I with 75 participants aged 3–17.[26][27]

In November 2021, Longcom began a phase II with 400 participants aged 3–17.[28]

Authorizations
  Full authorization
  Emergency authorization
  Allowed for travel
See also: List of COVID-19 vaccine authorizations § Zifivax

On 1 March 2021, Uzbekistan granted approval for ZF2001 (under tradename ZF-UZ-VAC 2001) after having taken part in the Phase III trials.[8] In March, Uzbekistan received 1 million doses and started vaccinations in April.[29] By June, a total of 6.5 million doses had been delivered.[30]

In March 2021, China approved of ZF2001 for emergency use after being approved by Uzbekistan earlier in the month.[7]

In June 2021, Malaysia's MyEG signed a letter of intent to purchase 10 million doses of the vaccine.[31]

On 7 September, the National Agency of Drug and Food Control of Indonesia (BPOM) published the emergency use authorization for Zifivax.[32]

On 10 January 2022, the National Agency of Drug and Food Control of Indonesia (BPOM) published the emergency use authorization for Zifivax as Booster for Sinovac.[33]

Research

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.[34]

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.[15] 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.[35]

References
  1. "Anhui Zhifei Longcom: RBD-Dimer – COVID19 Vaccine Tracker". covid19.trackvaccines.org. Retrieved 27 December 2020.
  2. "COVID-19 Vaccine: ZIFIVAX by Anhui Zhifei Longcom Biopharma, Institute of Microbiology Chinese Academy of Sciences". covidvax.org. Archived from the original on 30 January 2021. Retrieved 27 December 2020.
  3. "Fifth Chinese Covid-19 vaccine candidate ready to enter phase 3 trials". South China Morning Post. 20 November 2020. Retrieved 27 December 2020.
  4. Ying TP (7 December 2020). "MYEG to conduct phase 3 clinical trial for China's Covid-19 vaccine in Msia | New Straits Times". NST Online. Retrieved 27 December 2020.
  5. Hotez PJ, Bottazzi ME (January 2022). "Whole Inactivated Virus and Protein-Based COVID-19 Vaccines". Annual Review of Medicine. 73 (1): 55–64. doi:10.1146/annurev-med-042420-113212. PMID 34637324. S2CID 238747462.
  6. Zimmer C, Corum J, Wee SL (10 June 2020). "Coronavirus Vaccine Tracker". The New York Times. ISSN 0362-4331. Retrieved 27 December 2020.
  7. Liu R (15 March 2021). "China IMCAS's COVID-19 vaccine obtained emergency use approval in China". Reuters. Retrieved 15 March 2021.
  8. Mamatkulov M (1 March 2021). "Uzbekistan approves Chinese-developed COVID-19 vaccine". Reuters. Retrieved 2 March 2021.
  9. "China's production bottleneck 'could be eased with latest Covid-19 vaccine'". South China Morning Post. 17 March 2021. Retrieved 18 March 2021.
  10. "ZF-UZ-VAC-2001 vaccine to be produced in Uzbekistan". UzDaily.uz (in Russian). Retrieved 28 July 2021.
  11. Liu R (17 July 2021). "China Zhifei's COVID shot largely retains effect against Delta variant-lab study". Reuters. Retrieved 17 July 2021.
  12. "China's Zhifei says unit's COVID shot shows 81.76% efficacy in late-stage trial". Reuters. 27 August 2021.
  13. "New Chinese vaccine shows 82% effectiveness against serious Covid-19". The Straits Times. 27 August 2021. Retrieved 28 August 2021.
  14. Zhao X, Zheng A, Li D, Zhang R, Sun H, Wang Q, et al. (October 2021). "Neutralisation of ZF2001-elicited antisera to SARS-CoV-2 variants". The Lancet. Microbe. 2 (10): e494. doi:10.1016/S2666-5247(21)00217-2. PMC 8378832. PMID 34458880. S2CID 237246788.
  15. "What are protein subunit vaccines and how could they be used against COVID-19?". www.gavi.org. Retrieved 27 December 2020.
  16. "Another Chinese Covid-19 vaccine enters late-stage human trials with a plan to produce 300 million doses annually". Business Insider. Retrieved 27 December 2020.
  17. Clinical trial number NCT04445194 for "Phase I Clinical Study of Recombinant Novel Coronavirus Vaccine" at ClinicalTrials.gov
  18. 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
  19. 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
  20. Yang S, Li Y, Dai L, Wang J, He P, Li C, et al. (August 2021). "Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials". The Lancet. Infectious Diseases. 21 (8): 1107–1119. doi:10.1016/S1473-3099(21)00127-4. PMC 7990482. PMID 33773111.
  21. 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
  22. Reuters Staff (11 November 2020). "Uzbekistan to carry out late-stage trial of Chinese COVID-19 vaccine candidate". Reuters. Retrieved 27 December 2020. {{cite news}}: |author= has generic name (help)
  23. "Uzbekistan poised to start trials on Chinese COVID-19 vaccine | Eurasianet". eurasianet.org. Retrieved 27 December 2020.
  24. "Ecuador participará en ensayos de una vacuna china contra el covid-19". CNN (in Spanish). 29 December 2020. Retrieved 23 January 2021.
  25. "China's third vaccine enters Pakistan". The Nation. 15 February 2021. Retrieved 28 February 2021.
  26. "A randomized, blinded, placebo-controlled phase I clinical trial of recombinant New Coronavirus virus vaccine (CHO cells) in the safety and tolerability of healthy people aged 3 to 17 years of age". chictr.org.cn. Chinese Clinical Trial Registry. 7 July 2021. Retrieved 7 July 2021.
  27. "Recombinant New Coronavirus Vaccine (CHO Cells) to Prevent SARS-CoV-2 Phase I Clinical Trial (3~17 Years Old)". clinicaltrials.gov. United States National Library of Medicine. 14 July 2021. Retrieved 14 July 2021.
  28. "Clinical Trial of Immunogenicity Bridging of a Recombinant New Coronavirus（COVID-19）Vaccine (CHO Cell)". clinicaltrials.gov. United States National Library of Medicine. 5 November 2021. Retrieved 5 November 2021.
  29. "Uzbekistan receives 1 million doses of ZF-UZ-VAC 2001 vaccine". Kun.uz. Retrieved 28 March 2021.
  30. "Доставлен очередной миллион доз вакцины ZF-UZ-VAC2001". Газета.uz (in Russian). 30 June 2021. Retrieved 13 July 2021.
  31. "MyEG signs LOI to buy 10 million doses of Anhui Zhifei Covid-19 vaccine". The Star. Retrieved 28 August 2021.
  32. "BPOM Setujui Penggunaan Dalam Kedaruratan Vaksin Zifivax". Republika.co.id (in Indonesian). 7 October 2021. Retrieved 7 October 2021.
  33. "BPOM Terbitkan Izin Darurat untuk Booster, Pengguna Sinovac Bisa Gunakan Vaksin Zifivax Halaman all". 10 January 2022.
  34. Dai L, Zheng T, Xu K, Han Y, Xu L, Huang E, et al. (August 2020). "A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS". Cell. 182 (3): 722–733.e11. doi:10.1016/j.cell.2020.06.035. PMC 7321023. PMID 32645327.
  35. Dong Y, Dai T, Wei Y, Zhang L, Zheng M, Zhou F (October 2020). "A systematic review of SARS-CoV-2 vaccine candidates". Signal Transduction and Targeted Therapy. 5 (1): 237. doi:10.1038/s41392-020-00352-y. PMC 7551521. PMID 33051445.
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