Last updated

ZyCoV-D Logo.svg
Vaccine description
Target SARS-CoV-2
Vaccine type DNA
Clinical data
Routes of
ATC code
  • None
Legal status
Legal status

ZyCoV-D is a DNA plasmid-based COVID-19 vaccine developed by Indian pharmaceutical company Cadila Healthcare, with support from the Biotechnology Industry Research Assistance Council. It is approved for emergency use in India.



The vaccine contains a DNA plasmid vector that carries the gene encoding the spike protein of SARS-CoV-2. As with other DNA vaccines, the recipient's cells then produce the spike protein, eliciting a protective immune response. The plasmid also contains unmethylated CpG motifs to enhance its immunostimulatory properties. [1]

The plasmid is produced using E. coli cells. [1]

The vaccine is given as an intradermal injection using a spring-powered jet injector. [1] [2] This is because successful transfection of DNA vaccines requires traveling across both the cell plasma membrane and the nuclear membrane, [3] and using a conventional needle gives poor results and leads to low immunogenicity. [3] [4]

Clinical trials

Pre-clinical trials

In February 2020, Cadila Healthcare decided to develop a DNA plasmid based COVID-19 vaccine at their Vaccine Technology Centre (VTC) in Ahmedabad. [5] 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 . [1] [6] Thereafter, human trials for Phase I and II were approved by the regulator. [7]

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 1855 age range, with 28 days between each of the three doses. The trial found the vaccine to be "safe, well-tolerated and immunogenic". [8]

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. [9] [10] [11] The company reported that phase II trials were completed by November 2020. [12] [13]

Phase III trials

In November 2020, the company announced it would test the vaccine candidate on about 30,000 patients in Phase III trials. [13] In January 2021, the Drugs Controller General of India (DCGI) granted permission to conduct the Phase III clinical trials for 28,216 Indian participants in the 1299 age group. [14] [15] Of this, about 1,000 individuals were in the 1218 age group. [16] [17] Interim results from the phase III trials were made available in July 2021. [18]

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. [19] [20] [ unreliable medical source? ]


On 1 July 2021, Cadila Healthcare applied to the Drugs Controller General of India (DCGI), seeking approval for Restricted Use in Emergency Situation for the vaccine. [21] On 20 August 2021, the Subject Expert Committee of the Central Drugs Standard Control Organisation (CDSCO) recommended that the DCGI grant the approval, [22] which the DCGI then granted on the same day. [23]


On 23 April 2021, production of the ZyCoV-D vaccine was started, with a yearly capacity of 240 million doses. [24]

See also

Related Research Articles

Cadila Healthcare Indian multinational pharmaceutical company

Cadila Healthcare Limited is an Indian multinational pharmaceutical company headquartered in Ahmedabad, Gujarat, India primarily engaged in the manufacture of generic drugs. It ranked 100th in the Fortune India 500 list in 2020.

Arcturus Therapeutics is an American RNA medicines biotechnology company focused on the discovery, development and commercialization of therapeutics for rare diseases and infectious diseases. Arcturus has developed a novel, potent, and safe RNA therapeutics platform called LUNAR, a proprietary lipid-enabled delivery system for nucleic acid medicines including small interfering RNA (siRNA), messenger RNA (mRNA), gene editing RNA, DNA, antisense oligonucleotides (ASO), and microRNA.

Inovio Pharmaceuticals is an American biotechnology company focused on the discovery, development, and commercialization of synthetic DNA products for treating cancers and infectious diseases. In April 2020, Inovio was among some 100 companies, academic centers, or research organizations developing a vaccine candidate for treating people infected with COVID-19, with more than 170 total vaccine candidates in development.

COVID-19 vaccine Vaccine designed to provide acquired immunity against SARS-CoV-2

A COVID‑19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 (COVID‑19). Prior to the COVID‑19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This knowledge accelerated the development of various vaccine platforms during early 2020. The initial focus of SARS-CoV-2 vaccines was on preventing symptomatic, often severe illness. On 10 January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by 19 March, the global pharmaceutical industry announced a major commitment to address COVID-19. The COVID‑19 vaccines are widely credited for their role in reducing the spread, severity, and death caused by COVID-19.

CoronaVac Vaccine against COVID-19

CoronaVac, also known as the Sinovac COVID-19 vaccine, is an inactivated virus COVID-19 vaccine developed by the Chinese company Sinovac Biotech. It was Phase III clinical trialled in Brazil, Chile, Indonesia, the Philippines, and Turkey and relies on traditional technology similar to BBIBP-CorV and Covaxin, other inactivated-virus COVID-19 vaccines. CoronaVac does not need to be frozen and both the final product and the raw material for formulating CoronaVac can be transported refrigerated at 2–8 °C (36–46 °F), temperatures at which flu vaccines are kept.

Covaxin Vaccine against COVID-19

Covaxin is an inactivated virus-based COVID-19 vaccine developed by Bharat Biotech in collaboration with the Indian Council of Medical Research.

ZF2001 Vaccine against COVID-19

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. The vaccine candidate is in Phase III trials with 29,000 participants in China, Ecuador, Malaysia, Pakistan, and Uzbekistan.

Janssen COVID-19 vaccine Vaccine against COVID-19

The Janssen COVID-19 vaccine or Johnson & Johnson COVID-19 vaccine is a COVID-19 vaccine that was developed by Janssen Vaccines in Leiden, Netherlands, and its Belgian parent company Janssen Pharmaceuticals, subsidiary of American company Johnson & Johnson.

COVID-19 vaccination in India Immunisation programme against COVID-19 in India

India began administration of COVID-19 vaccines on 16 January 2021. As of 10 October 2021, India has administered over 947 million doses overall, including first and second doses of the currently-approved vaccines.

History of COVID-19 vaccine development Scientific work to develop a vaccine for COVID-19

COVID-19's caused virus, SARS-CoV-2, was isolated in late 2019. Its genetic sequence was published on 11 January 2020, triggering an urgent international response to prepare for an outbreak and hasten development of a preventive COVID-19 vaccine. Since 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments. By June 2020, tens of billions of dollars were invested by corporations, governments, international health organizations, and university research groups to develop dozens of vaccine candidates and prepare for global vaccination programs to immunize against COVID‑19 infection. According to the Coalition for Epidemic Preparedness Innovations (CEPI), the geographic distribution of COVID‑19 vaccine development shows North American entities to have about 40% of the activity, compared to 30% in Asia and Australia, 26% in Europe, and a few projects in South America and Africa.

CureVac COVID-19 vaccine Vaccine candidate against COVID-19

The CureVac COVID-19 vaccine is a COVID-19 vaccine candidate developed by CureVac N.V. and the Coalition for Epidemic Preparedness Innovations (CEPI). The vaccine showed inadequate results in its Phase III trials with only 47% efficacy.

SCB-2019 Vaccine candidate against COVID-19

SCB-2019 is a protein subunit COVID-19 vaccine developed by Clover Biopharmaceuticals using an adjuvant from Dynavax technologies. Positive results of Phase I trials for the vaccine were published in The Lancet and the vaccine completed enrollment of 29,000 participants in Phase II/III trials in July 2021. In September 2021, SCB-2019 announced Phase III results showing 67% efficacy against all cases of COVID-19 and 79% efficacy against all cases of the Delta variant. Additionally, the vaccine was 84% effective against moderate cases and 100% effective against hospitalization.

BBV154 Vaccine candidate against COVID-19

BBV154 is an intranasal COVID-19 vaccine candidate developed by Bharat Biotech, American company Precision Virologics and the Washington University School of Medicine in St Louis, Missouri ,United States.

Sinopharm WIBP COVID-19 vaccine Vaccine against COVID-19

The Sinopharm WIBP COVID-19 vaccine, also known as WIBP-CorV, is one of two inactivated virus COVID-19 vaccines developed by Sinopharm. Peer-reviewed results show WIBP-CorV 72.8% effective against symptomatic cases and 100% against severe cases. The other inactivated virus COVID-19 vaccine developed by Sinopharm is BBIBP-CorV which is comparably more successful. 1 billion doses are expected to be produced per year.

Viral vector vaccine Type of vaccine

A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material coding for a desired antigen into the recipient's host cells. As of April 2021, six viral vector vaccines have been authorized for use in human at least one country: four COVID-19 vaccines and two Ebola vaccines.

Walvax COVID-19 vaccine Vaccine candidate against COVID-19

ARCoV, also known as the Walvax COVID-19 vaccine, is an mRNA COVID-19 vaccine candidate developed by Walvax Biotechnology, Suzhou Abogen Biosciences, and the PLA Academy of Military Science. It is approved for Phase III trials in China, Mexico, Indonesia, and Nepal.

Corbevax Vaccine candidate against COVID-19 and infertility

Corbevax or BioE COVID-19, is a COVID-19 vaccine candidate developed by Indian biopharmacutical firm Biological E. Limited (BioE), the Baylor College of Medicine in Houston, United States, and American company Dynavax Technologies (DVAX). It is a protein subunit vaccine.

HGC019 Vaccine candidate against COVID-19

HGC019 is a mRNA based COVID-19 vaccine candidate being developed by Gennova Biopharmaceuticals and HDT Biotech Corporation with active support from Department of Biotechnology, India.

COVID-19 vaccine clinical research

COVID-19 vaccine clinical research is the clinical research on COVID-19 vaccines, including their efficacy, effectiveness and safety. There are 22 vaccines authorized for use by national governments, with six vaccines being approved for emergency or full use by at least one WHO-recognised stringent regulatory authority; and five of them are in Phase IV. 204 vaccines under clinical trials that have not yet been authorized. There are also nine clinical trials on heterologous vaccination courses.

Soberana Plus

Soberana Plus, technical name FINLAY-FR-1A, is a COVID-19 candidate vaccine produced by the Finlay Institute, a Cuban epidemiological research institute.


  1. 1 2 3 4 Dey A, Chozhavel Rajanathan TM, Chandra H, Pericherla HP, Kumar S, Choonia HS, et al. (July 2021). "Immunogenic potential of DNA vaccine candidate, ZyCoV-D against SARS-CoV-2 in animal models". Vaccine. 39 (30): 4108–4116. doi:10.1016/j.vaccine.2021.05.098. PMC   8166516 . PMID   34120764.
  2. Raghavan P (2 July 2021). "Explained: How ZyCov-D vaccine works, how it is different". The Indian Express .
  3. 1 2 Rauch S, Jasny E, Schmidt KE, Petsch B (2018). "New Vaccine Technologies to Combat Outbreak Situations". Frontiers in Immunology. 9: 1963. doi: 10.3389/fimmu.2018.01963 . PMC   6156540 . PMID   30283434.
  4. Jiang J, Ramos SJ, Bangalore P, Fisher P, Germar K, Lee BK, et al. (June 2019). "Integration of needle-free jet injection with advanced electroporation delivery enhances the magnitude, kinetics, and persistence of engineered DNA vaccine induced immune responses". Vaccine. 37 (29): 3832–3839. doi: 10.1016/j.vaccine.2019.05.054 . PMID   31174938.
  5. "Zydus Cadila launches a fast tracked programme to develop vaccine for the novel coronavirus, 2019-nCoV (COVID-19)" (PDF). www.zyduscadila.com. Cadila Healthcare.
  6. Yadav PD, Kumar S, Agarwal K, Jain M, Patil DR, Maithal K, et al. (3 February 2021). "Assessment of immunogenicity and protective efficacy of ZyCoV-D DNA vaccine candidates in Rhesus macaques against SARS-CoV-2 infection". bioRxiv. doi:10.1101/2021.02.02.429480. S2CID   231885750.
  7. "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". ctri.nic.in. Clinical Trials Registry India. 15 December 2020. CTRI/2020/07/026352. Archived from the original on 22 November 2020.
  8. Momin T, Kansagra K, Patel H, Sharma S, Sharma B, Patel J, et al. (August 2021). "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". EClinicalMedicine . Lancet Publishing Group. 38: 101020. doi:10.1016/j.eclinm.2021.101020. ISSN   2589-5370. PMC   8285262 . PMID   34308319.
  9. "COVID-19 vaccine progress and FDA approvals for Zydus Cadila". Generics and Biosimilar Initiative . Pro Pharma Communications International. 13 November 2021. Archived from the original on 4 December 2020. Retrieved 20 August 2021.
  10. "Zydus Cadila's ZyCov-D vaccine found to be 'safe and immunogenic'". @businessline. The Hindu. 24 December 2020.
  11. Rawat K, Kumari P, Saha L (February 2021). "COVID-19 vaccine: A recent update in pipeline vaccines, their design and development strategies". European Journal of Pharmacology. 892: 173751. doi: 10.1016/j.ejphar.2020.173751 . PMC   7685956 . PMID   33245898.
  12. Pilla V (3 November 2020). "Covid Vaccine: Zydus Cadila completes phase-2 trial, to submit data in November". Moneycontrol . Network18 Group. Archived from the original on 3 November 2020. Retrieved 20 August 2021.
  13. 1 2 Thacker T (7 November 2020). "Zydus Cadila to test ZyCoV-D on 30,000 patients in Phase-3 trials". The Economic Times.
  14. "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". ctri.nic.in. Clinical Trials Registry India. 1 June 2021. CTRI/2021/01/030416. Archived from the original on 10 April 2021.
  15. "DBT-BIRAC supported indigenously developed DNA Vaccine Candidate by Zydus Cadila, approved for Phase III clinical trials". pib.gov.in. Press Information Bureau. 3 January 2021.
  16. "Zydus seeks emergency-use nod for plasmid DNA vaccine". @businessline. The Hindu. 1 July 2021.
  17. Kaul R (18 August 2021). "Covid vaccine for children in India by September, says ICMR-NIV director". Hindustan Times . HT Media. Archived from the original on 18 August 2021. Retrieved 20 August 2021.
  18. "Zycov-D, India's first COVID-19 vaccine for those above 12, gets nod". The Hindu. The Hindu Group. 20 August 2021. Archived from the original on 20 August 2021. Retrieved 20 August 2021.
  19. "Zydus applies to the DCGI for EUA to launch ZyCoV-D, the world's first Plasmid DNA vaccine for COVID-19" (PDF). Cadila Healthcare (Press release). 1 July 2021. Retrieved 1 July 2021.
  20. "Zydus Cadila jab shows 66.6% efficacy, seeks regulatory nod". livemint. 2 July 2021. Retrieved 2 July 2021.
  21. "Emergency use nod sought for ZyCoV-D". The Hindu. 1 July 2021.
  22. Sharma, Milan (20 August 2021). "Expert panel recommends Zydus Cadila's three-dose Covid vaccine ZyCoV-D for EUA". India Today . New Delhi: Living Media. Archived from the original on 20 August 2021. Retrieved 20 August 2021.
  23. "Zydus Cadila's 3-Dose Covid Vaccine ZyCoV-D Gets DCGI's Approval For EUA". Outlook India . 20 August 2021. Archived from the original on 20 August 2021. Retrieved 20 August 2021.
  24. Staff Writer (24 April 2021). "Cadila Healthcare starts production of Covid vaccine candidate". mint. Retrieved 27 April 2021.

Further reading