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.[1][2] As of December 2020, the vaccine candidate was 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 namesRBD-Dimer
Routes of
administration		Intramuscular
ATC code
  • None
Identifiers
DrugBank
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ZF2001 employs technology similar to other protein-based vaccines in Phase III trials from Novavax, Vector Institute, and Medicago.[5] It is administered in 3 doses over a period of 2 months.[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.[6] Phase II results published in The Lancet on the three dose administration showed seroconversion rates of neutralizing antibodies of between 92% to 97%.[9]

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.[10]

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.[11] 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.[12] Subunit vaccines are delivered alongside adjuvants and booster doses may be required.[11]

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.[6]

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.[13]

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.[14] In August, an additional Phase II trial was launched with 50 participants aged 60 and above.[15][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.[9]

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.[16][17]

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.[4]

In December, Uzbekistan began a year-long Phase III trial of ZF2001 with 5,000 volunteers between 18 and 59.[18][19]

In December, Ecuador's Minister of Health, Juan Carlos Zevallos announced Phase III trials would involve between 5,000 and 8,000 volunteers.[20]

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.[21]

Discussions to begin Phase III trials are also underway in Indonesia.[17][22]

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.[23] 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.[24] 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.[23]

Manufacturing

The company's vaccine manufacturing facility was put into use in September.[17] In February 2021, Pu Jiang, General Manager of Zhifei Longcom, said the company had an annual production capacity of 1 billion doses.[6]

Marketing and deployment

Authorization and eligibility by country
  Full authorization
  • None
  Emergency authorization

On March 1, 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 plans to start mass vaccinations on April 5.[27]

On March 15, China approve of ZF2001 for limited use after being approved for use by Uzbekistan earlier in the month.[7]

References
  1. "Anhui Zhifei Longcom: RBD-Dimer – COVID19 Vaccine Tracker". covid19.trackvaccines.org. Retrieved 27 December 2020.
  2. "COVID-19 Vaccine: RBD-Dimer by Anhui Zhifei Longcom Biopharma, Institute of Microbiology Chinese Academy of Sciences". covidvax.org. 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. Zimmer C, Corum J, Wee SL (10 June 2020). "Coronavirus Vaccine Tracker". The New York Times. ISSN 0362-4331. Retrieved 27 December 2020.
  6. "China's production bottleneck 'could be eased with latest Covid-19 vaccine'". South China Morning Post. 17 March 2021. Retrieved 18 March 2021.
  7. Liu, Roxanne (15 March 2021). "China IMCAS's COVID-19 vaccine obtained emergency use approval in China". Reuters. Retrieved 15 March 2021.
  8. Mamatkulov, Mukhammadsharif (1 March 2021). "Uzbekistan approves Chinese-developed COVID-19 vaccine". Reuters. Retrieved 2 March 2021.
  9. Yang, Shilong; Li, Yan; Dai, Lianpan; Wang, Jianfeng; He, Peng; Li, Changgui; Fang, Xin; Wang, Chenfei; Zhao, Xiang; Huang, Enqi; Wu, Changwei (24 March 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. 0 (0). doi:10.1016/S1473-3099(21)00127-4. ISSN 1473-3099. PMC 7990482.
  10. 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.
  11. "What are protein subunit vaccines and how could they be used against COVID-19?". www.gavi.org. Retrieved 27 December 2020.
  12. 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.
  13. Clinical trial number NCT04445194 for "Phase I Clinical Study of Recombinant Novel Coronavirus Vaccine" at ClinicalTrials.gov
  14. 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
  15. 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
  16. 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
  17. "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.
  18. Reuters Staff (11 November 2020). "Uzbekistan to carry out late-stage trial of Chinese COVID-19 vaccine candidate". Reuters. Retrieved 27 December 2020.
  19. "Uzbekistan poised to start trials on Chinese COVID-19 vaccine | Eurasianet". eurasianet.org. Retrieved 27 December 2020.
  20. "Ecuador participará en ensayos de una vacuna china contra el covid-19". CNN (in Spanish). 29 December 2020. Retrieved 23 January 2021.
  21. "China's third vaccine enters Pakistan". The Nation. 15 February 2021. Retrieved 28 February 2021.
  22. "Covid vaccine tracker: How do the leading jabs compare?". www.ft.com. 23 December 2020. Retrieved 27 December 2020.
  23. Liu, Roxanne (3 February 2021). "Sinopharm's COVID-19 vaccine remained active against S.Africa variant, effect reduced - lab study". Reuters. Retrieved 29 March 2021.
  24. Huang, Baoying; Dai, Lianpan; Wang, Hui; Hu, Zhongyu; Yang, Xiaoming; Tan, Wenjie; Gao, George F. (2 February 2021). "Neutralization of SARS-CoV-2 VOC 501Y.V2 by human antisera elicited by both inactivated BBIBP-CorV and recombinant dimeric RBD ZF2001 vaccines". bioRxiv: 2021.02.01.429069. doi:10.1101/2021.02.01.429069.
  25. Mamatkulov, Mukhammadsharif (1 March 2021). "Uzbekistan approves Chinese-developed COVID-19 vaccine". Reuters. Retrieved 2 March 2021.
  26. "Uzbekistan certifies Chinese vaccine to fight against COVID-19". China Daily. 2 March 2021. Retrieved 8 March 2021.
  27. uz, Kun. "Uzbekistan receives 1 million doses of ZF-UZ-VAC 2001 vaccine". Kun.uz. Retrieved 28 March 2021.
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