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ZyCoV-D COVID-19 Vaccine

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November 28, 2021
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ZyCoV-D COVID-19 Vaccine Description

ZyCoV-D is India's first indigenously developed plasma DNA vaccine against COVID-19. In addition, ZyCoV-D is the world's first Plasmid DNA Vaccine authorized for COVID-19.

The ZyCoV-D vaccine was developed by Zydus Cadila using a non-replicating and non-integrating plasmid carrying the novel coronavirus gene and approved by the Drugs Controller General of India (DCGI) to conduct late-stage clinical trials. 

ZyCoV-D is a three-dose intradermal vaccine, which is applied using The PharmaJet® needle-free system, Tropis®, which can significantly reduce any side effects. Also, being a plasmid DNA vaccine, ZyCoV-D doesn't display vector-based immunity concerns, says the Company.  A painless, needle-free injector delivers the vaccine in a narrow fluid stream into the skin.

DNA vaccines are composed of bacterial plasmids with a gene encoding for the protein of interest and transcription promoter and terminator. The plasmid gains entry in multiple cells such as myocytes, keratinocytes, and antigen-presenting cells. It enters the nucleus as an episome without getting integrated into the host cell DNA. Once the plasmids enter the nuclei of cells, they are converted into mRNA, which travels to the main body of the cell, the cytoplasm, and is translated into the spike protein itself.

Using the host cell's transcription and translation machinery, the inserted gene gets translated into antigen. A protein expressed by plasmid-transfected cells (APC) is likely to be expressed within the cell and folded in its native configuration. The antigen is recognized by APCs and further induces antibodies and cellular response.

The Company says the plug-and-play technology on which the plasmid DNA platform can be easily adapted to mutations in the coronavirus. The Plasmid DNA platform also allows generating new constructs quickly to deal with mutations in the virus, such as those already occurring. In addition, the DNA platform is known to have better vaccine stability and lower cold chain requirements, which would make it easier to store and transport to remote parts of the country.

Zydus Cadila announced it had applied for Emergency Use Authorization (EUA) to the office of the DCGI for ZyCoV-D on July 1, 2021. On August 20, 2021, Zydus Cadila announced that the Company had received the EUA from the DCGI. The Company also plans to seek approval for the two-dose regimen of the vaccine.

India's National Biopharma Mission has supported the ZyCov-D vaccine candidate under the Biotechnology Industry Research Assistance Council. Accordingly, a PSU under the DBT was issued. The Accession Number is DB15892. Clinical trial listing.

Registered Trials listing of the ZyCoV-D vaccine, as of November 10, 2021.

Zydus Cadila is headquartered in Ahmedabad, India, Zydus Corporate Park, Scheme No. 63, Survey No. 536, Nr. Vaishnodevi Circle, S.G. Highway, and ranks 4th in the Indian pharmaceutical industry. The group has manufacturing sites and research facilities spread across Gujarat, Maharashtra, Goa, Himachal Pradesh, Sikkim in India, the USA, and Brazil. The Zydus Research Centre is the dedicated research arm of the Zydus Group. With its team of over 400 research professionals, ZRC spearheads the group's quest of creating healthier and happier communities globally. Vaccine Technology Centre of Zydus Cadila has a wide range of capabilities in developing and manufacturing viral, toxoid, polysaccharide, conjugate, and other subunit vaccines for unmet needs.

ZyCoV-D COVID-19 Vaccine Indication

ZyCoV-D COVID-19 Vaccine is indicated to prevent COVID-19, the disease caused by the SARS-CoV-2 virus. ZyCoV-D exhibited robust immunogenicity, tolerability, and safety profile in earlier adaptive Phase I/II clinical trials. In addition, an independent Data Safety Monitoring Board has monitored both the Phase I/II and Phase III clinical trials. India has authorized ZyCoV-D COVID-19 Vaccine for adolescents older than 12 years of age.

The journal Nature says 'ZyCoV-D vaccine heralds a wave of DNA vaccines for various diseases that are undergoing clinical trials around the world.' The JAMA Network published an article on October 12, 2021 - India’s New COVID-19 DNA Vaccine for Adolescents and Adults Is a First. The vaccine contains plasmid DNA, circular strands of genetic material that enter the host cells’ nuclei, where they’re converted into mRNA. The mRNA then travels out of the nuclei into the cytoplasm and is translated into the SARS-CoV-2 spike protein.

ZyCoV-D COVID-19 Vaccine Construct

Gene sequence was submitted to GeneArt, Thermo Fisher Scientific, and codon-optimized full-length Spike (S) region of SARS-CoV-2 virus with IgE signal sequence was synthesized. The chemically synthesized Spike (S) gene region preceded by IgE signal sequence was inserted into the pVAX-1 plasmid DNA vaccine vector (Thermo Fisher Scientific). Subsequently, the plasmid DNA construct was transformed in DH5-αTM chemically competent cells (Thermo Fisher Scientific). After the heat shock transformation step, E. coli clones carrying the plasmid DNA constructs were isolated by plating on an LB agar plate containing Kanamycin antibiotic. Single colonies were picked and inoculated in flasks containing LB broth from Hi-Media with Kanamycin. Flasks were incubated in a 37 °C incubator shaker at 225 rpm for 20 Hrs. Culture from each clone was used for plasmid isolation using a miniprep plasmid isolation kit. Restriction digestion was carried out with BamH1, Nhe1, and Apa1 for all constructs to check the expected band releases of inserts to select the positive clones. Positive clones were selected for preparation of glycerol stocks and stored at −70 °C. In-vitro expression of DNA vaccine candidate was checked by transfection of the same in Vero cell line.

DNA vaccines have been under development since the 1990s. The challenge for DNA vaccines is that they need to make it all the way to the cell nucleus. DNA vaccines struggled to induce potent immune responses in clinical trials, which is why they had been approved for use as vaccines only in animals.

ZyCoV-D COVID-19 Vaccine Dosage

The vaccine is a three-dose vaccination for a total of 6 mg. The Company has also evaluated a two-dose regimen for the ZyCoV-D vaccine using a 3 mg dose per dose. The immunogenicity results of the two-dose were equivalent to the current three-dose regimen in a clinical trial.

ZyCoV-D COVID-19 Vaccine Side Effects

A study published by The Lancet EClinical Medicine on July 16, 2021, found a majority of solicited AEs reported were after the first dose of vaccine, while the second and third doses of vaccination were found to be well-tolerated. The ZyCoV-D Phase 1 safety data further suggest that the vaccine could be a safe booster as there was no increase in the frequency of side effects after the third dose compared to the first dose, an important aspect for the safety profile of SARS-CoV-2 vaccines. One attractive feature of DNA vaccines, like ZyCoV-D, is that the immunizations could be boosted without significant limitations such as dosing-incremented toxicities or anti-vector responses, and additional boosting with other DNA vaccines have resulted in higher levels of cellular and humoral immune responses without increased toxicity. The ZyCoV-D vaccine is found to be safe, well-tolerated, and immunogenic in the Phase 1 trial.

ZyCoV-D COVID-19 Vaccine Storage

ZyCoV-D is stored at 2-8 oC but has shown good stability at temperatures of 25oC for at least three months. The thermostability of the vaccine will help in easy transportation and storage of the vaccine and reduce any cold chain breakdown challenges leading to vaccine wastage.

ZyCoV-D COVID-19 Vaccine News

November 26, 2021 - Media reported 2,37,530 doses of the ZyCoV-D vaccine have been released after being tested by the Central Drug Laboratory in Kasauli, India.

November 24, 2021 - Enzychem Lifesciences in South Korea and Cadila Healthcare entered into a manufacturing license and technology transfer agreement for the plasmid DNA-based Covid vaccine, ZyCoV-D.

November 18, 2021 - Local media reported Zydus Cadila will supply 1 crore doses of ZyCoV-D to the Government of India by December 2021.

November 14, 2021 - Local media in India reported: “ZyCov-D, which has been cleared by India’s drug regulator for those aged 12 years and above, will be given only to adults as of now under the national COVID vaccination drive,” an official source said.

November 7, 2021 - Local media reported Zydus Cadila's ZyCoV-D is likely to be included in the nationwide vaccination drive, with the Union government ordering 10 million doses of the vaccine.

October 28, 2021 - ANI reported India intends to procure two crore doses of the ZyCoV-D vaccine in November 2021.

October 26, 2021 - Local media reported a comprehensive priority list of children with comorbidities is being worked out prior to the launch of ZyCoV-D in India, according to a senior official from the Centre’s Covid-19 working group of the National Technical Advisory Group on Immunisation. To assist in developing recommendations for use of vaccines against COVID-19, the WHO's SAGE proposes a Roadmap for Prioritizing Uses of COVID-19 Vaccines that considers priority populations for vaccination based on the epidemiologic setting.

October 11, 2021 - Local media in India reported the ZyCoV-D vaccine will be made available to private sector hospitals across the country.

September 11, 2021 - India's local media reported that Zydus Cadila's coronavirus vaccine ZyCoV-D would likely be launched in October 2021.

September 2, 2021 - The journal Nature published an article: India's DNA COVID vaccine is a world-first – more are coming. Both DNA and mRNA vaccines have been under development since the 1990s, says Weiner. The challenge for DNA vaccines is that they need to make it all the way to the cell nucleus, unlike mRNA vaccines, which need to get to the cytoplasm.

August 20, 2021 - Zydus Cadila announced India's Subject Expert Committee of Central Drugs Standard Control Organisation recommended an emergency use authorization for Zydus Cadila's three-dose plasma DNA COVID-19 vaccine ZyCoV-D. The Company applied for this authorization on July 1, 2021.

August 11, 2021 - Zydus Cadila published Investor Presentation Q1FY22. The Company confirmed 'a second vaccine candidate ZyCoV-MV targeted at COVID-19, completed Pragmatic Clinical Trials and non-human primate immunogenicity study is going on at present.'

July 16, 2021 - The Lancet published a research paper: 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. Interpretation: ZyCoV-D vaccine is found to be safe, well-tolerated, and immunogenic in the Phase 1 trial. Our findings suggest that the DNA vaccine warrants further investigation.

July 9, 2021 - Zydus Cadila Healthcare is conducting a trial across 59 sites for children between 12 and 18 and adults aged up to 65 for ZyCoV-D.

July 2, 2021 - News18 reported: ZyCoV-D: Decoding the Science behind India's Plasmid DNA Vaccine & What Makes it Special.

July 1, 2021 - Zydus Cadila announced that the Company has applied for Emergency Use Authorization to the office of Drug Controller General of India for ZyCoV-D, its Plasmid DNA Vaccine against COVID-19. The Company has conducted the largest clinical trial for its COVID-19 vaccine in India in over 50 centers. This was also the first time that any COVID-19 vaccine has been tested in the adolescent population in the 12-18 years age group in India. Around 1,000 subjects were enrolled in this age group, and the vaccine was found to be safe and very well tolerated. The tolerability profile was similar to that seen in the adult population. Primary efficacy of 66.6% has been attained for symptomatic RT-PCR positive cases in the interim analysis. In comparison, no moderate case of COVID-19 disease was observed in the vaccine arm post administration of the third dose suggesting 100% efficacy for moderate disease. Furthermore, no severe cases or deaths due to COVID-19 occurred in the vaccine arm after administering the second dose of the vaccine.

June 27, 2021 - Local media reported The National Technical Advisory Group on Immunisation chairman Dr. NK Arora said that the ZyCoV-D COVID-19 Vaccine developed for adolescents above the age of 12 could be available by August 2021.

June 19, 2021 - Local media in India reported Zydus Cadila might apply to the Drugs Controller General of India for an emergency use authorization for its ZyCoV-D vaccine candidate.

May 20, 2021 - Local media reported that Jeevan Rekha Hospital in Belagavi has successfully conducted the first-phase clinical trials of the country's second indigenously-developed COVID-19 vaccine, ZyCoV-D, 20 children between the age of 12 and 18 years. None of the children who underwent the clinical trials had any side effects or other health complications two months after the vaccines were administered to them, said Dr. Amit Bhate, Director of Jeevan Rekha Hospital.

May 19, 2021 - In an interview with DH, Zydus Group's managing director Sharvil Patel spoke about ZyCoV-D, the second homegrown Covid-19 vaccine in India.

May 10, 2021 - Zydus Wellness Ltd. announced results for the fourth quarter ended March 31, 2021. The Company reported a 23.9% growth in consolidated net sales, which stood at Rs. 6008 mn.

April 23, 2021 - Reuters reported Cadila Healthcare has started producing its COVID-19 vaccine, for which it will soon seek emergency use authorization. The Company may produce 240 million vaccine doses a year.

April 22, 2021 - Local media reported the Company is conducting phase 3 efficacy trials on a three-dose regimen of its DNA plasmid technology-based Covid-19 vaccine.

February 5, 2021 - European Journal of Pharmacology, Volume 892, published: COVID-19 vaccine: A recent update in pipeline vaccines, design, and development strategies.

February 3, 2021 - Preprint study: Assessment of immunogenicity and protective efficacy of ZyCoV-D DNA vaccine candidates in Rhesus macaques against SARS-CoV-2 infection. The study demonstrated the vaccine candidate's immunogenicity and protective efficacy, ZyCoV-D, in rhesus macaques.

February 2, 2021 - Assessment of immunogenicity and protective efficacy of ZyCoV-D DNA vaccine candidates in Rhesus macaques against SARS-CoV-2 infection.

January 26, 2021 - A non-peer-reviewed study: Immunogenic Potential of DNA Vaccine candidate, ZyCoV-D against SARS-CoV-2 in Animal Models. The preliminary animal study demonstrates that the candidate DNA vaccine induces antibody response, including neutralizing antibodies against SARS-CoV-2, and provided Th-1 response as evidenced by elevated IFN-γ levels.

January 3, 2021 - Zydus Cadila announced that it would be starting Phase III clinical trials of its plasmid DNA vaccine to prevent COVID-19, ZyCoV-D, after receiving permissions from the DCGI. Speaking on the development, Mr. Pankaj R. Patel, Chairman of the Zydus Group, said, "We are reaching a critical milestone in our vaccine development program and towards our goal of helping people fight the pandemic with an indigenously discovered, safe, and efficacious vaccine. The launch of the Phase 3 trial will determine the efficacy of our vaccine in preventing COVID-19 which continues to pose a major threat the world over."

December 24, 2020 - Zydus Cadila announced that its plasmid DNA vaccine to prevent COVID-19, ZyCoV-D, was found to be safe, well-tolerated, and immunogenic in Phase I/II clinical trials. The Company plans to initiate Phase III clinical trials in around 30,000 volunteers upon receiving necessary approvals.

July 9, 2020 - COVID-19 Vaccine Development Update.

ZyCoV-D COVID-19 Vaccine Clinical Trials

CTRI/2021/01/030416 - A phase III, randomized, multi-center, double-blind, placebo-controlled study to evaluate the efficacy, safety, and immunogenicity of Novel Corona Virus -2019-nCov vaccine candidate of M/s Cadila Healthcare Limited. Interim results from Phase 3 clinical trials in over 28,000 volunteers: Demonstrates Safety and Efficacy in the interim data of the largest vaccine trial so far in India for COVID-19. The study was carried out in more than 50 clinical sites spread across the country and during the peak of the second wave of COVID-19, reaffirming the vaccine's efficacy against the new mutant strains, especially the delta variant. The study also shows that ZyCoV-D is safe for children aged 12 to 18 years. The PharmaJet®, a needle-free applicator, ensures painless intradermal vaccine delivery. The study was last updated on August 24, 2021.

Phase 1/2 study: CTRI/2020/07/026352 

The Lancet published the results of this study; the ZyCoV-D vaccine is found to be safe, well-tolerated, and immunogenic in the Phase 1 trial. However, our findings suggest that the DNA vaccine warrants further investigation.

'Out of 126 individuals screened for eligibility. Forty-eight subjects (mean age 34·9 years) were enrolled and vaccinated in the Phase 1 study. Overall, 12/48 (25%) subjects reported at least one AE (i.e., combined solicited and unsolicited) during the study. There were no deaths or serious adverse events reported in Phase 1 of the study. The proportion of subjects who seroconverted based on IgG titers on day 84 was 4/11 (36·36%), 4/12 (33·33%), 10/10 (100·00%) and 8/10 (80·00%) in the treatment Arm 1 (1 mg: Needle), Arm 2 (1 mg: NFIS), Arm 3 (2 mg: Needle) and Arm 4 (2 mg: NFIS), respectively.'

Phase 1/2 study: CTRI/2021/03/032051

Clinical Trials

No clinical trials found