ZyCoV-D COVID-19 Vaccine Description
ZyCoV-D is India's first indigenously developed plasma DNA vaccine candidate against COVID-19. The ZyCoV-D vaccine was developed by Zydus Cadila and approved by the Drugs Controller General of India to conduct late-stage clinical trials.
ZyCov-D was developed on a DNA platform using a non-replicating and non-integrating plasmid carrying the novel coronavirus gene, making it very safe. In addition, ZyCoV-D is a three-dose intradermal vaccine, which is applied using The PharmaJet® needle-free system, Tropis®, which can also significantly reduce any side effects.
Also, being a plasmid DNA vaccine, ZyCoV-D doesn’t have any problem with vector-based immunity, says the company. 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. 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. ZyCoV-D is stored at 2-8 C but has shown good stability at temperatures of 25C 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.
On August 20, 2021, Zydus Cadila announced that the company had received the Emergency Use Authorization (EUA) from the Drug Controller General of India (DCGI) for ZyCoV-D, the world’s first Plasmid DNA Vaccine for COVID-19. The company also plans to seek approval for the two-dose regimen of the vaccine.
Mr. Pankaj R. Patel, Chairman, Cadila Healthcare Ltd., stated in a press statement issued on August 20, 2021, “This is a historic milestone with ZyCoV-D, a product of Indian innovation becoming the world’s first DNA vaccine being offered for human use and supporting the world’s largest immunization drive. We are particularly happy that our vaccine will contribute to this fight against COVID-19 and enable the country to vaccinate a larger population, especially in 12-18 years. I want to thank all the researchers, clinical trial investigators, volunteers, and the regulators who have supported this endeavor.”
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.
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. ZyCoV-D is a three-dose, intradermal vaccine applied using a needle-free system, Tropis, which can significantly reduce application side effects.
ZyCoV-D COVID-19 Vaccine Dosage
The vaccine is evaluating 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 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
September 11, 2021 - India's local media reported that Zydus Cadila's coronavirus vaccine ZyCoV-D would likely be launched in early 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