Biology:ZF2001

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Short description: Vaccine against COVID-19
ZF2001
Vaccine description
Target diseaseSARS-CoV-2
TypeProtein subunit
Clinical data
Trade namesRBD-Dimer
Routes of
administration		Intramuscular
ATC code
  • None
Identifiers
DrugBank

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 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. 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.[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

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 started vaccinations in April.[25] By May, a total of 3 million doses had been delivered.[26]

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

References

  1. ↑ 1.0 1.1 "Anhui Zhifei Longcom: RBD-Dimer – COVID19 Vaccine Tracker". https://covid19.trackvaccines.org/vaccines/27/. 
  2. ↑ "COVID-19 Vaccine: RBD-Dimer by Anhui Zhifei Longcom Biopharma, Institute of Microbiology Chinese Academy of Sciences" (in en). https://covidvax.org/covid19-vaccine/AnhuiZhifei/Adjuvanted-recombinant-protein-Anhui-Zhifei-Longcom-Biopharma-Institute-of-Microbiology-Chinese-Acad. 
  3. ↑ "Fifth Chinese Covid-19 vaccine candidate ready to enter phase 3 trials" (in en). 2020-11-20. https://www.scmp.com/news/china/science/article/3110690/coronavirus-chinas-cnbg-set-review-covid-19-vaccine-phase-3. 
  4. ↑ 4.0 4.1 "MYEG to conduct phase 3 clinical trial for China's Covid-19 vaccine in Msia | New Straits Times" (in en). 2020-12-07. https://www.nst.com.my/news/nation/2020/12/647456/myeg-conduct-phase-3-clinical-trial-chinas-covid-19-vaccine-msia. 
  5. ↑ "Coronavirus Vaccine Tracker" (in en-US). The New York Times. 2020-06-10. ISSN 0362-4331. https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html. 
  6. ↑ 6.0 6.1 6.2 6.3 "China’s production bottleneck ‘could be eased with latest Covid-19 vaccine’" (in en). 2021-03-17. https://www.scmp.com/news/china/science/article/3125809/chinas-production-bottleneck-could-be-eased-latest-covid-19. 
  7. ↑ 7.0 7.1 Liu, Roxanne (2021-03-15). "China IMCAS's COVID-19 vaccine obtained emergency use approval in China" (in en). Reuters. https://www.reuters.com/article/health-coronavirus-china-vaccine-idUSL4N2LD3BZ. 
  8. ↑ 8.0 8.1 Mamatkulov, Mukhammadsharif (2021-03-01). "Uzbekistan approves Chinese-developed COVID-19 vaccine" (in en). Reuters. https://www.reuters.com/article/uzbekistan-china-coronavirus-vaccine-idINS0N2IK00P. 
  9. ↑ 9.0 9.1 Yang, Shilong; Li, Yan; Dai, Lianpan; Wang, Jianfeng; He, Peng; Li, Changgui; Fang, Xin; Wang, Chenfei et al. (2021-03-24). "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" (in English). The Lancet Infectious Diseases 0 (0). doi:10.1016/S1473-3099(21)00127-4. ISSN 1473-3099. 
  10. ↑ "A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS". Cell 182 (3): 722–733.e11. August 2020. doi:10.1016/j.cell.2020.06.035. PMID 32645327. 
  11. ↑ 11.0 11.1 "What are protein subunit vaccines and how could they be used against COVID-19?" (in en). https://www.gavi.org/vaccineswork/what-are-protein-subunit-vaccines-and-how-could-they-be-used-against-covid-19. 
  12. ↑ "A systematic review of SARS-CoV-2 vaccine candidates". Signal Transduction and Targeted Therapy 5 (1): 237. October 2020. doi:10.1038/s41392-020-00352-y. 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. ↑ 17.0 17.1 17.2 "Another Chinese Covid-19 vaccine enters late-stage human trials with a plan to produce 300 million doses annually". https://www.businessinsider.in/science/health/news/another-chinese-covid-19-vaccine-enters-late-stage-human-trials-with-a-plan-to-produce-300-million-doses-annually/articleshow/79320575.cms. 
  18. ↑ Reuters Staff (2020-11-11). "Uzbekistan to carry out late-stage trial of Chinese COVID-19 vaccine candidate" (in en). Reuters. https://www.reuters.com/article/us-health-coronavirus-uzbekistan-china-idUSKBN27R1FX. 
  19. ↑ "Uzbekistan poised to start trials on Chinese COVID-19 vaccine | Eurasianet" (in en). https://eurasianet.org/uzbekistan-poised-to-start-trials-on-chinese-covid-19-vaccine. 
  20. ↑ "Ecuador participará en ensayos de una vacuna china contra el covid-19" (in es). 2020-12-29. https://cnnespanol.cnn.com/2020/12/28/ecuador-participara-en-ensayos-de-una-de-las-vacunas-chinas-contra-el-covid-19/. 
  21. ↑ "China's third vaccine enters Pakistan" (in en). 2021-02-15. https://nation.com.pk/15-Feb-2021/china-s-third-vaccine-enters-pakistan. 
  22. ↑ "Covid vaccine tracker: How do the leading jabs compare?" (in en-GB). 2020-12-23. https://www.ft.com/content/ac5e5ef8-bccb-482b-9f8d-0dab5cac6f9a. 
  23. ↑ 23.0 23.1 Liu, Roxanne (2021-02-03). "Sinopharm's COVID-19 vaccine remained active against S.Africa variant, effect reduced - lab study" (in en). Reuters. https://www.reuters.com/article/us-health-coronavirus-china-vaccine-idUSKBN2A30DT. 
  24. ↑ Huang, Baoying; Dai, Lianpan; Wang, Hui; Hu, Zhongyu; Yang, Xiaoming; Tan, Wenjie; Gao, George F. (2021-02-02). "Neutralization of SARS-CoV-2 VOC 501Y.V2 by human antisera elicited by both inactivated BBIBP-CorV and recombinant dimeric RBD ZF2001 vaccines" (in en). bioRxiv: 2021.02.01.429069. doi:10.1101/2021.02.01.429069. https://www.biorxiv.org/content/10.1101/2021.02.01.429069v1. 
  25. ↑ uz, Kun. "Uzbekistan receives 1 million doses of ZF-UZ-VAC 2001 vaccine" (in en). https://kun.uz/en/news/2021/03/27/uzbekistan-receives-1-million-doses-of-zf-uz-vac-2001-vaccine. 
  26. ↑ Romakayeva, Klavdiya (2021-05-18). "Uzbekistan receives third batch of Chinese-Uzbek COVID-19 vaccine" (in en). https://en.trend.az/casia/uzbekistan/3425381.html. 

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