View source for Medicine:ZyCoV-D

{{Short description|Vaccine candidate against COVID-19}}
{{pp-30-500 |small=yes}}
<!-- recommended structure: see WP:MEDORDER and WP:DRUGLIKE -->
{{Use Indian English|date=March 2021}}
{{Infobox drug
| Verifiedfields     = 
| verifiedrevid      = 
| type               = vaccine
| image              = ZyCoV-D Logo.svg
| image2             = 
| caption            = 
| target             = [[Biology:Severe acute respiratory syndrome coronavirus 2|SARS-CoV-2]]
| vaccine_type       = DNA
| tradename          = 
| MedlinePlus        = 
| pregnancy_AU       = 
| pregnancy_AU_comment = 
| pregnancy_category = 
| routes_of_administration = [[Medicine:Intradermal injection|Intradermal]]
| ATC_prefix         = None <!-- scheduled to be J07BX03 in 2022 -->
| ATC_suffix         = 
| ATC_supplemental   = 
| legal_AU           = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_CA           = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK           = 
| legal_status       = Full list of ZyCoV-D authorizations
| CAS_number_Ref     = 
| CAS_number         = 
| DrugBank_Ref       = 
| DrugBank           = DB15892
| PubChem            = 
| ChemSpiderID_Ref   = 
| ChemSpiderID       = 
}}

'''ZyCoV-D''' is a [[Medicine:DNA vaccine|DNA plasmid]]-based [[Medicine:COVID-19 vaccine|COVID-19 vaccine]] developed by {{wipe|India}}n pharmaceutical company Cadila Healthcare, with support from the Biotechnology Industry Research Assistance Council. It is approved for emergency use in India.

== Technology ==
The vaccine contains a DNA [[Biology:Plasmid|plasmid]] [[Biology:Vectors in gene therapy#Non-viral methods|vector]] that carries the gene encoding the spike protein of [[Biology:SARS-CoV-2|SARS-CoV-2]]. As with other [[Medicine:DNA vaccine|DNA vaccine]]s, the recipient's cells then produce the spike protein, eliciting a protective immune response.  The plasmid also contains [[Biology:DNA methylation|unmethylated]] [[Biology:CpG site|CpG]] motifs to enhance its immunostimulatory properties.<ref name="preclinical-report" />

The plasmid is produced using [[Biology:Escherichia coli|''E. coli'']] cells.<ref name="preclinical-report" />

The vaccine is given as an [[Medicine:Intradermal injection|intradermal injection]] using a spring-powered [[Engineering:Jet injector|jet injector]].<ref name="preclinical-report" /><ref>{{cite news|date=2 July 2021|title=Explained: How ZyCov-D vaccine works, how it is different|language=en|work=The Indian Express|url=https://indianexpress.com/article/explained/explained-how-zycov-d-works-how-it-is-different-7385000/|vauthors=Raghavan P}}</ref>  This is because successful [[Biology:Transfection|transfection]] of DNA vaccines requires traveling across both the [[Biology:Cell membrane|cell plasma membrane]] and the [[Biology:Nuclear envelope|nuclear membrane]],<ref name="Frontiers">{{cite journal | vauthors = Rauch S, Jasny E, Schmidt KE, Petsch B | title = New Vaccine Technologies to Combat Outbreak Situations | language = English | journal = Frontiers in Immunology | volume = 9 | pages = 1963 | date = 2018 | pmid = 30283434 | pmc = 6156540 | doi = 10.3389/fimmu.2018.01963 | doi-access = free }}</ref> and using a conventional needle gives poor results and leads to low immunogenicity.<ref name="Frontiers" /><ref>{{cite journal | vauthors = Jiang J, Ramos SJ, Bangalore P, Fisher P, Germar K, Lee BK, Williamson D, Kemme A, Schade E, McCoy J, Muthumani K, Weiner DB, Humeau LM, Broderick KE | display-authors = 6 | title = Integration of needle-free jet injection with advanced electroporation delivery enhances the magnitude, kinetics, and persistence of engineered DNA vaccine induced immune responses | journal = Vaccine | volume = 37 | issue = 29 | pages = 3832–3839 | date = June 2019 | pmid = 31174938 | doi = 10.1016/j.vaccine.2019.05.054 | doi-access = free }}</ref>

==Clinical trials==
===Pre-clinical trials===
In February 2020, Cadila Healthcare decided to develop a [[Medicine:DNA vaccine|DNA plasmid]] based [[Medicine:COVID-19 vaccine|COVID-19 vaccine]] at their Vaccine Technology Centre (VTC) in Ahmedabad.<ref>{{cite web | title=Zydus Cadila launches a fast tracked programme to develop vaccine for the novel coronavirus, 2019-nCoV (COVID-19) |url=https://zyduscadila.com/public/pdf/pressrelease/Zydus_Cadila_launches_a_fast_tracked_programme_to_develop_vaccine_for_the_novel_coronavirus_2019-nCoVCOVID-19).pdf |website=www.zyduscadila.com |publisher=Cadila Healthcare}}</ref> The vaccine candidate was able to pass the pre-clinical trials on animal models successfully. A report of the study was made available via ''bioRxiv'' and later published in the journal ''Vaccine''.<ref name="preclinical-report">{{cite journal | vauthors = Dey A, Chozhavel Rajanathan TM, Chandra H, Pericherla HP, Kumar S, Choonia HS, Bajpai M, Singh AK, Sinha A, Saini G, Dalal P, Vandriwala S, Raheem MA, Divate RD, Navlani NL, Sharma V, Parikh A, Prasath S, Sankar Rao M, Maithal K | display-authors = 6 | title = Immunogenic potential of DNA vaccine candidate, ZyCoV-D against SARS-CoV-2 in animal models | journal = Vaccine | volume = 39 | issue = 30 | pages = 4108–4116 | date = July 2021 | pmid = 34120764 | pmc = 8166516 | doi = 10.1016/j.vaccine.2021.05.098|issn=0264-410X }}</ref><ref>{{cite journal | vauthors=Yadav PD, Kumar S, Agarwal K, Jain M ,Patil DR, Maithal K, Mathapati B, Giri S, Mohandas S, Shete A, Sapkal G, Patil DY, Dey A, Chandra H, Deshpande G, Gupta N, Nyayanit D, Kaushal H, Sahay R, Tripathy A, Jain R, Kumar A, Sarkale P, Baradkar S, Rajanathan C, Raju HP, Patel S, Shah N, Dwivedi P, Singh D, Abraham P| display-authors = 6 |title=Assessment of immunogenicity and protective efficacy of ZyCoV-D DNA vaccine candidates in Rhesus macaques against SARS-CoV-2 infection |journal=bioRxiv |date=3 February 2021 |doi=10.1101/2021.02.02.429480| s2cid = 231885750}}</ref> Thereafter, human trials for Phase I and II were approved by the regulator.<ref>{{Cite web | website=ctri.nic.in|publisher=[[Medicine:Clinical Trials Registry – India|Clinical Trials Registry India]]| title=A prospective, randomized, adaptive, phase I/II clinical study to evaluate the safety and immunogenicity of Novel Corona Virus −2019-nCov vaccine candidate of M/s Cadila Healthcare Limited by intradermal route in healthy subjects |id=CTRI/2020/07/026352 |url=http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=45306| url-status=live| archive-url=https://web.archive.org/web/20201122022620/http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=45306| archive-date=22 November 2020| date=15 December 2020}}</ref>

===Phase I and II trials===
Phase I trials of the vaccine candidate started on 15 July 2020 and continued until October 2020. The vaccine candidate was tested on 48 healthy individuals in the 18&ndash;55 age range, with 28 days between each of the three doses. The trial found the vaccine to be "safe, well-tolerated and immunogenic".<ref name="MominEtAl2021">{{cite journal |vauthors=Momin T, Kansagra K, Patel H, Sharma S, Sharma B, Patel J, Mittal R, Sanmukhani J, Maithal K, Dey A, Chandra H, Rajanathan CT, Pericherla HP, Kumar P, Narkhede A, Parmar D |display-authors=6 |title=Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India |journal=eClinicalMedicine|publisher=Lancet Publishing Group|date=August 2021 |volume=38 |pages=101020 |doi=10.1016/j.eclinm.2021.101020 |pmid=34308319 |pmc=8285262 |url=https://doi.org/10.1016/j.eclinm.2021.101020 |issn=2589-5370}}</ref>

Cadila Healthcare began phase II trials of the vaccine candidate from 6 August 2021 with over 1,000 volunteers as part of the adaptive Phase I/II multi-centric, dose escalation, randomised, double-blind placebo controlled method.<ref name="GaBI2021">{{cite web|title=COVID-19 vaccine progress and FDA approvals for Zydus Cadila|work=Generics and Biosimilar Initiative|date=2021-11-13|url=https://www.gabionline.net/generics/news/COVID-19-vaccine-progress-and-FDA-approvals-for-Zydus-Cadila|publisher=Pro Pharma Communications International|archive-date=2020-12-04|archive-url=https://web.archive.org/web/20201204113608/https://www.gabionline.net/generics/news/COVID-19-vaccine-progress-and-FDA-approvals-for-Zydus-Cadila|url-status=live|access-date=2021-08-20}}</ref><ref>{{cite news |title=Zydus Cadila's ZyCov-D vaccine found to be 'safe and immunogenic' |url=https://www.thehindubusinessline.com/news/zydus-cadilas-zycov-d-vaccine-found-to-be-safe-and-immunogenic/article33412776.ece |work=@businessline |agency=The Hindu |date=24 December 2020 |language=en}}</ref><ref>{{cite journal | vauthors = Rawat K, Kumari P, Saha L | title = COVID-19 vaccine: A recent update in pipeline vaccines, their design and development strategies | journal = European Journal of Pharmacology | volume = 892 | pages = 173751 | date = February 2021 | pmid = 33245898 | pmc = 7685956 | doi = 10.1016/j.ejphar.2020.173751 | doi-access = free }}</ref> The company reported that phase II trials were completed by November 2020.<ref name="Pilla2020">{{cite news|vauthors=Pilla V|url=https://www.moneycontrol.com/news/business/companies/covid-vaccine-zydus-cadila-completes-phase-2-trial-to-submit-data-in-november-6058811.html|date=2020-11-03|title=Covid Vaccine: Zydus Cadila completes phase-2 trial, to submit data in November|work=Moneycontrol|publisher=Network18 Group|access-date=2021-08-20|url-status=live|archive-date=2020-11-03|archive-url=https://web.archive.org/web/20201103081829/https://www.moneycontrol.com/news/business/companies/covid-vaccine-zydus-cadila-completes-phase-2-trial-to-submit-data-in-november-6058811.html}}</ref><ref name="Thacker2020" />

===Phase III trials===
In November 2020, the company announced it would test the vaccine candidate on about 30,000 patients in Phase III trials.<ref name="Thacker2020">{{cite news | vauthors = Thacker T |title=Zydus Cadila to test ZyCoV-D on 30,000 patients in Phase-3 trials |url= https://economictimes.indiatimes.com/industry/healthcare/biotech/pharmaceuticals/zydus-cadila-to-test-zycov-d-on-30000-patients-in-phase-3-trials/articleshow/79088859.cms |work=The Economic Times |date=7 November 2020}}</ref> In January 2021, the [[Medicine:Drugs Controller General of India|Drugs Controller General of India]] (DCGI) granted permission to conduct the Phase III clinical trials for 28,216 Indian participants in the 12&ndash;99 age group.<ref>{{Cite web | website=ctri.nic.in|publisher=[[Medicine:Clinical Trials Registry – India|Clinical Trials Registry India]]| title=A phase III, randomized, multi-centre, double blind, placebo controlled, study to evaluate efficacy, safety and immunogenicity of Novel Corona Virus -2019-nCov vaccine candidate of M/s Cadila Healthcare Limited. |id=CTRI/2021/01/030416 |url=http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=51254&EncHid=&userName=ZyCoV-D| url-status=live| archive-url=https://web.archive.org/web/20210410010006/http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=51254&EncHid=&userName=ZyCoV-D| archive-date=10 April 2021| date=1 June 2021}}</ref><ref>{{cite news |title=DBT-BIRAC supported indigenously developed DNA Vaccine Candidate by Zydus Cadila, approved for Phase III clinical trials |url=https://pib.gov.in/Pressreleaseshare.aspx?PRID=1685838 |work=pib.gov.in |publisher=Press Information Bureau |date=3 January 2021}}</ref> Of this, about 1,000 individuals were in the 12&ndash;18 age group.<ref>{{cite news |title=Zydus seeks emergency-use nod for plasmid DNA vaccine |url=https://www.thehindubusinessline.com/companies/zydus-seeks-emergency-use-nod-for-plasmid-dna-vaccine/article35084124.ece |work=@businessline |publisher=The Hindu |date=1 July 2021 |language=en}}</ref><ref name="Kaul2021">{{cite news|vauthors=Kaul R|title=Covid vaccine for children in India by September, says ICMR-NIV director|work=Hindustan Times|publisher=HT Media|date=2021-08-18<!--UTC; 2021-08-19 IST-->|url-status=live|access-date=2021-08-20|archive-date=2021-08-18|archive-url=https://web.archive.org/web/20210818201310/https://www.hindustantimes.com/india-news/covid-vaccine-for-children-in-india-by-september-says-icmr-niv-director-101629284019229.html|url=https://www.hindustantimes.com/india-news/covid-vaccine-for-children-in-india-by-september-says-icmr-niv-director-101629284019229.html}}</ref> Interim results from the phase III trials were made available in July 2021.<ref name="Hindu202108">{{cite news|url=https://www.thehindu.com/news/national/zycov-d-indias-first-covid-19-vaccine-for-those-above-12-gets-nod/article36021251.ece|title=Zycov-D, India's first COVID-19 vaccine for those above 12, gets nod|date=2021-08-20|access-date=2021-08-20|archive-date=20 August 2021|archive-url=https://archive.today/2021.08.20-203731/https://www.thehindu.com/news/national/zycov-d-indias-first-covid-19-vaccine-for-those-above-12-gets-nod/article36021251.ece|url-status=live|work=The Hindu|publisher=The Hindu Group}}</ref>

On 1 July 2021, Cadila Healthcare reported the efficacy to be 66.6% against symptomatic COVID-19 and 100% against moderate or severe disease in its interim analysis of its phase 3 trial data.<ref>{{cite press release|title=Zydus applies to the DCGI for EUA to launch ZyCoV-D, the world's first Plasmid DNA vaccine for COVID-19|url=https://zyduscadila.com/public/pdf/pressrelease/ZyCoV_D_Press_Release_1_7_2021.pdf|date=1 July 2021|access-date=1 July 2021|website=Cadila Healthcare}}</ref><ref>{{cite web|date=2 July 2021|title=Zydus Cadila jab shows 66.6% efficacy, seeks regulatory nod|url=https://www.livemint.com/companies/news/zydus-cadila-applies-for-eua-for-covid-19-vaccine-zycovd-11625152872531.html|access-date=2 July 2021|website=livemint}}</ref><ref>{{cite journal | vauthors = Khobragade A, Bhate S, Ramaiah V, Deshpande S, Giri K, Phophle H, Supe P, Godara I, Revanna R, Nagarkar R, Sanmukhani J, Dey A, Rajanathan TM, Kansagra K, Koradia P | display-authors = 6 | title = Efficacy, safety, and immunogenicity of the DNA SARS-CoV-2 vaccine (ZyCoV-D): the interim efficacy results of a phase 3, randomised, double-blind, placebo-controlled study in India | journal = Lancet | volume = 399 | issue = 10332 | pages = 1313–1321 | date = April 2022 | pmid = 35367003 | pmc = 8970574 | doi = 10.1016/S0140-6736(22)00151-9 }}</ref><!-- Do not remove {{Unreliable medical source}} untill WP:MEDRS is available -->

===Authorizations===
{{image frame|content={{Graph:Map|scale=50|defaultValue=gainsboro
|IN=dodgerblue
}}
|caption=
{{leftlegend|blueviolet|Full authorization}}
{{leftlegend|dodgerblue|Emergency authorization}}
}}

On 1 July 2021, Cadila Healthcare applied to the [[Medicine:Drugs Controller General of India|Drugs Controller General of India]] (DCGI), seeking approval for Restricted Use in Emergency Situation for the vaccine.<ref>{{cite news |title=Emergency use nod sought for ZyCoV-D |url=https://www.thehindu.com/news/national/emergency-use-nod-sought-for-zycov-d/article35086029.ece |work=The Hindu |date=1 July 2021 |language=en-IN}}</ref> On 20 August 2021, the Subject Expert Committee of the [[Organization:Central Drugs Standard Control Organisation|Central Drugs Standard Control Organisation]] (CDSCO) recommended that the DCGI grant the approval,<ref name="Sharma2021">{{cite news| vauthors = Sharma M |location=New Delhi|title=Expert panel recommends Zydus Cadila's three-dose Covid vaccine ZyCoV-D for EUA|url=https://www.indiatoday.in/coronavirus-outbreak/story/expert-panel-recommends-zydus-cadila-three-dose-covid-vaccine-zycov-d-for-eua-1843331-2021-08-20|archive-url=https://archive.today/2021.08.20-153907/https://www.indiatoday.in/coronavirus-outbreak/story/expert-panel-recommends-zydus-cadila-three-dose-covid-vaccine-zycov-d-for-eua-1843331-2021-08-20|date=2021-08-20|access-date=2021-08-20|archive-date=20 August 2021|url-status=live|work=India Today|publisher=Living Media}}</ref> which the DCGI then granted on the same day.<ref name="OutlookIndia2021">{{cite news|title=Zydus Cadila's 3-Dose Covid Vaccine ZyCoV-D Gets DCGI's Approval For EUA|url=https://www.outlookindia.com/website/story/india-news-govt-panel-recommends-emergency-use-authorisation-to-zydus-cadilas-3-dose-covid-vaccine/392099|work=Outlook India|date=2021-08-20|access-date=2021-08-20|archive-date=2021-08-20|archive-url=https://web.archive.org/web/20210820160841/https://www.outlookindia.com/website/story/india-news-govt-panel-recommends-emergency-use-authorisation-to-zydus-cadilas-3-dose-covid-vaccine/392099}}</ref>

==Deployment==
On 23 April 2021, production of the ZyCoV-D vaccine was started, with a yearly capacity of 240 million doses.<ref>{{Cite web|author=Staff Writer|date=2021-04-24|title=Cadila Healthcare starts production of Covid vaccine candidate|url=https://www.livemint.com/companies/news/cadila-healthcare-starts-production-of-covid-vaccine-candidate-11619244017749.html|access-date=2021-04-27|website=mint|language=en}}</ref>

== See also ==
*COVID-19 vaccination in India

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Kutzler MA, Weiner DB | title = DNA vaccines: ready for prime time? | journal = Nature Reviews. Genetics | volume = 9 | issue = 10 | pages = 776–88 | date = October 2008 | pmid = 18781156 | pmc = 4317294 | doi = 10.1038/nrg2432 | doi-access = free }}
* {{cite journal | vauthors = Liu MA | title = A Comparison of Plasmid DNA and mRNA as Vaccine Technologies | journal = Vaccines | volume = 7 | issue = 2 | page = 37 | date = April 2019 | pmid = 31022829 | pmc = 6631684 | doi = 10.3390/vaccines7020037 | doi-access = free }}
* {{cite journal | vauthors = Silveira MM, Moreira GM, Mendonça M | title = DNA vaccines against COVID-19: Perspectives and challenges | journal = Life Sciences | volume = 267 | pages = 118919 | date = February 2021 | pmid = 33352173 | pmc = 7749647 | doi = 10.1016/j.lfs.2020.118919 | doi-access = free }}
{{refend}}

== External links ==
* {{cite news | vauthors = Raghavan P | date = 8 July 2021 |title=Explained: How ZyCov-D vaccine works, how it is different |url=https://indianexpress.com/article/explained/explained-how-zycov-d-works-how-it-is-different-7385000/ |work=The Indian Express |language=en}}
* {{cite news | date = 2 July 2021 |title=What is ZyCov-D, world's first DNA vaccine for Covid? |url=https://www.hindustantimes.com/india-news/what-is-zycov-d-world-s-first-dna-vaccine-for-covid-101625162617692.html |work=Hindustan Times |language=en}}


{{Vaccines}}


{{DEFAULTSORT:ZyCoV-D}}
[[Category:Clinical trials]]

{{Sourceattribution|ZyCoV-D|1}}