ZF2001: Difference between revisions
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In February 2021, lab studies of serum samples taken from recipients of [[BBIBP-CorV]] and ZF2001 retained neutralizing activity against the [[SARS-CoV-2 Beta variant|Beta variant]] although with weaker activity than against the original virus.<ref name=":10">{{Cite news|last=Liu|first=Roxanne|date=2021-02-03|title=Sinopharm's COVID-19 vaccine remained active against S.Africa variant, effect reduced - lab study|language=en|work=Reuters|url=https://www.reuters.com/article/us-health-coronavirus-china-vaccine-idUSKBN2A30DT|url-status=live|access-date=2021-03-29}}</ref> 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.<ref>{{Cite journal|last1=Huang|first1=Baoying|last2=Dai|first2=Lianpan|last3=Wang|first3=Hui|last4=Hu|first4=Zhongyu|last5=Yang|first5=Xiaoming|last6=Tan|first6=Wenjie|last7=Gao|first7=George F.|date=2021-02-02|title=Neutralization of SARS-CoV-2 VOC 501Y.V2 by human antisera elicited by both inactivated BBIBP-CorV and recombinant dimeric RBD ZF2001 vaccines|url=https://www.biorxiv.org/content/10.1101/2021.02.01.429069v1|journal=bioRxiv|language=en|pages=2021.02.01.429069|doi=10.1101/2021.02.01.429069|s2cid=231834094}}</ref> 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.<ref name=":10" /> |
In February 2021, lab studies of serum samples taken from recipients of [[BBIBP-CorV]] and ZF2001 retained neutralizing activity against the [[SARS-CoV-2 Beta variant|Beta variant]] although with weaker activity than against the original virus.<ref name=":10">{{Cite news|last=Liu|first=Roxanne|date=2021-02-03|title=Sinopharm's COVID-19 vaccine remained active against S.Africa variant, effect reduced - lab study|language=en|work=Reuters|url=https://www.reuters.com/article/us-health-coronavirus-china-vaccine-idUSKBN2A30DT|url-status=live|access-date=2021-03-29}}</ref> 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.<ref>{{Cite journal|last1=Huang|first1=Baoying|last2=Dai|first2=Lianpan|last3=Wang|first3=Hui|last4=Hu|first4=Zhongyu|last5=Yang|first5=Xiaoming|last6=Tan|first6=Wenjie|last7=Gao|first7=George F.|date=2021-02-02|title=Neutralization of SARS-CoV-2 VOC 501Y.V2 by human antisera elicited by both inactivated BBIBP-CorV and recombinant dimeric RBD ZF2001 vaccines|url=https://www.biorxiv.org/content/10.1101/2021.02.01.429069v1|journal=bioRxiv|language=en|pages=2021.02.01.429069|doi=10.1101/2021.02.01.429069|s2cid=231834094}}</ref> 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.<ref name=":10" /> |
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In July 2021, lab studies showed ZF2001 largely retained its neutralizing effect against [[Delta variant]] with a slight reduction. |
In July 2021, lab studies showed ZF2001 largely retained its neutralizing effect against [[Delta variant]] with a slight reduction. Serum samples from people vaccinated with ZF2001 showed a 1.2-fold reduction in neutralising effect compared against the original variant of COVID-19.<ref name=":9" /><ref name=":12">{{Cite journal|last=Zhao|first=Xin|last2=Zheng|first2=Anqi|last3=Li|first3=Dedong|last4=Zhang|first4=Rong|last5=Sun|first5=Huan|last6=Wang|first6=Qihui|last7=Gao|first7=George F.|last8=Han|first8=Pengcheng|last9=Dai|first9=Lianpan|date=2021-08-20|title=Neutralisation of ZF2001-elicited antisera to SARS-CoV-2 variants|url=https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00217-2/abstract|journal=The Lancet Microbe|language=English|volume=0|issue=0|doi=10.1016/S2666-5247(21)00217-2|issn=2666-5247}}</ref> |
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In the same study, the scientists found that ZF2001 also retained neutralizing effect against B.1.429 (Epsilon), B.1.351(Beta), P.1(Gamma), B.1.525(Eta), B.1.617.1(Kappa), the neutralizing titers decrease ranged from 1.1 fold to 2.1 fold, but the neutralizing efficacy were still good. |
In the same study, the scientists found that ZF2001 also retained neutralizing effect against B.1.429 (Epsilon), B.1.351(Beta), P.1(Gamma), B.1.525(Eta), B.1.617.1(Kappa), the neutralizing titers decrease ranged from 1.1 fold to 2.1 fold, but the neutralizing efficacy were still good.<ref name=":12" /> |
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== Manufacturing == |
== Manufacturing == |
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Revision as of 06:12, 25 August 2021
| Vaccine description | |
|---|---|
| Target | SARS-CoV-2 |
| Vaccine type | Protein subunit |
| Clinical data | |
| Trade names | ZIFIVAX |
| Routes of administration | Intramuscular |
| ATC code |
|
| Identifiers | |
| DrugBank | |
| Part of a series on the |
| COVID-19 pandemic |
|---|
 |
|
.svg){kind=small} COVID-19 portal |
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] 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 of finished product is expected to be one billion doses a year in China[6] and 200 million in Uzbekistan.[9] By July, 100 million doses had been administered in China and Uzbekistan.[10] Phase II results published in The Lancet on the three dose administration showed seroconversion rates of neutralizing antibodies of between 92% to 97%.[11]
Efficacy
In February 2021, lab studies of serum samples taken from recipients of BBIBP-CorV and ZF2001 retained neutralizing activity against the Beta variant although with weaker activity than against the original virus.[12] 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.[13] 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.[12]
In July 2021, lab studies showed ZF2001 largely retained its neutralizing effect against Delta variant with a slight reduction. Serum samples from people vaccinated with ZF2001 showed a 1.2-fold reduction in neutralising effect compared against the original variant of COVID-19.[10][14]
In the same study, the scientists found that ZF2001 also retained neutralizing effect against B.1.429 (Epsilon), B.1.351(Beta), P.1(Gamma), B.1.525(Eta), B.1.617.1(Kappa), the neutralizing titers decrease ranged 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.[6] 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.[6]
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.[9]
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.[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.[11]
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.[20][16]
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.[21][22]
In December, Ecuador's Minister of Health, Juan Carlos Zevallos announced Phase III trials would involve between 5,000 and 8,000 volunteers.[23]
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.[24]
Discussions to begin Phase III trials are also underway in Indonesia.[16][25]
Children and adolescents trial
In July 2021, Longcom began a randomized, blinded, placebo-controlled phase I with 75 participants aged 3-17.[26][27]
Authorizations
Full authorization
Emergency authorization
Allowed for travel | |||
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.[28] By June, a total of 6.5 million doses had been delivered.[29]
On March 15, China approved of ZF2001 for emergency use after being approved by Uzbekistan earlier in the month.[7]
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.[30]
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.[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.[31]
References
- ^ a b "Anhui Zhifei Longcom: RBD-Dimer – COVID19 Vaccine Tracker". covid19.trackvaccines.org. Retrieved 27 December 2020.
- ^ "COVID-19 Vaccine: ZIFIVAX by Anhui Zhifei Longcom Biopharma, Institute of Microbiology Chinese Academy of Sciences". covidvax.org. Retrieved 27 December 2020.
- ^ "Fifth Chinese Covid-19 vaccine candidate ready to enter phase 3 trials". South China Morning Post. 20 November 2020. Retrieved 27 December 2020.
- ^ a b 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.
- ^ Zimmer C, Corum J, Wee SL (10 June 2020). "Coronavirus Vaccine Tracker". The New York Times. ISSN 0362-4331. Retrieved 27 December 2020.
- ^ a b c d "China's production bottleneck 'could be eased with latest Covid-19 vaccine'". South China Morning Post. 17 March 2021. Retrieved 18 March 2021.
- ^ a b Liu, Roxanne (15 March 2021). "China IMCAS's COVID-19 vaccine obtained emergency use approval in China". Reuters. Retrieved 15 March 2021.
{{cite news}}: CS1 maint: url-status (link) - ^ a b Mamatkulov, Mukhammadsharif (1 March 2021). "Uzbekistan approves Chinese-developed COVID-19 vaccine". Reuters. Retrieved 2 March 2021.
{{cite news}}: CS1 maint: url-status (link) - ^ a b UzDaily. "ZF-UZ-VAC-2001 vaccine to be produced in Uzbekistan". UzDaily.uz (in Russian). Retrieved 28 July 2021.
- ^ a b Liu, Roxanne (17 July 2021). "China Zhifei's COVID shot largely retains effect against Delta variant-lab study". Reuters. Retrieved 17 July 2021.
- ^ a b 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. doi:10.1016/S1473-3099(21)00127-4. ISSN 1473-3099. PMC 7990482. PMID 33773111.
- ^ a b 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.
{{cite news}}: CS1 maint: url-status (link) - ^ 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. S2CID 231834094.
- ^ a b Zhao, Xin; Zheng, Anqi; Li, Dedong; Zhang, Rong; Sun, Huan; Wang, Qihui; Gao, George F.; Han, Pengcheng; Dai, Lianpan (20 August 2021). "Neutralisation of ZF2001-elicited antisera to SARS-CoV-2 variants". The Lancet Microbe. 0 (0). doi:10.1016/S2666-5247(21)00217-2. ISSN 2666-5247.
- ^ a b "What are protein subunit vaccines and how could they be used against COVID-19?". www.gavi.org. Retrieved 27 December 2020.
- ^ a b c "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.
- ^ 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
- ^ 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) - ^ "Uzbekistan poised to start trials on Chinese COVID-19 vaccine | Eurasianet". eurasianet.org. Retrieved 27 December 2020.
- ^ "Ecuador participará en ensayos de una vacuna china contra el covid-19". CNN (in Spanish). 29 December 2020. Retrieved 23 January 2021.
- ^ "China's third vaccine enters Pakistan". The Nation. 15 February 2021. Retrieved 28 February 2021.
- ^ "Covid vaccine tracker: How do the leading jabs compare?". www.ft.com. 23 December 2020. Retrieved 27 December 2020.
- ^ "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.
{{cite web}}: CS1 maint: url-status (link) - ^ "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.
{{cite web}}: CS1 maint: url-status (link) - ^ uz, Kun. "Uzbekistan receives 1 million doses of ZF-UZ-VAC 2001 vaccine". Kun.uz. Retrieved 28 March 2021.
- ^ "Доставлен очередной миллион доз вакцины ZF-UZ-VAC2001". Газета.uz (in Russian). 30 June 2021. Retrieved 13 July 2021.
- ^ 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.
- ^ 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.
