ZyCoV-D COVID-19 Vaccine For 2022
ZyCoV-D is India's first indigenously developed plasma DNA vaccine targeted against COVID-19. In addition, ZyCoV-D is the world's first Plasmid DNA Vaccine authorized for COVID-19 prevention.
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 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 immunization 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 integrating 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.
The inserted gene gets translated into antigen using the host cell's transcription and translation machinery. 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. As a result, DNA-based vaccines do not need a SARS-CoV-2 virus strain, unlike the inactivated vaccines that require viruses in killed or inactivated forms. In addition, the DNA platform is known to have better vaccine stability and lower cold chain requirements, making 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. In addition, the Lancet published phase 1 study results that found the ZyCoV-D vaccine safe, well-tolerated and immunogenic. On August 20, 2021, Zydus Cadila announced that the Company had received the EUA from the DCGI. On February 2, 2022, Zydus announced that the Company had started delivering ZyCoV-D supplies to the Government of India. On April 15, 2022, local media reported ZyCoV-D had received the subject expert committee's approval for a two-dose regimen. On April 22, 2022, the media reported the SEC recommended the grant of EUA to Cadila for ZyCoV-D for an additional dose of 3mg with a two-jab inoculation schedule 28 days apart for those aged 12 years and above. Presently, ZyCoV-D is approved for a 2mg three-dose vaccination schedule. And on April 26, 2022, The DCGI authorized EUA for ZyCoV-D as a two-dose vaccine.
The Lancet published a phase 3 study interim analysis on April 2, 2022, finding ZyCoV-D efficacious, safe, and immunogenic. The ZyCoV-D vaccine efficacy was 66.6% (95% CI 47·6–80·7).
India's National Biopharma Mission has supported the ZyCov-D vaccine candidate under the Biotechnology Industry Research Assistance Council. The Accession Number is DB15892. Registered clinical trials are listing the ZyCoV-D vaccine as of April 2022.
Zydus Lifesciences Ltd. is headquartered in Ahmedabad, India, Zydus Corporate Park, Scheme No. 63, Survey No. 536, Nr. Vaishnodevi Circle, S.G. Highway, 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 over 400 research professionals, ZRC spearheads the group's global quest to create healthier and happier communities. 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 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. As a result, India 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 undergoing clinical trials worldwide.' In addition, 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.
In April 2022, health minister Dr. Mansukh Mandaviya said the Central Drugs Standard Control Organization authorized two doses of ZyCoV-D for those above 12 years of age.
In a tweet posted on January 16, 2022, Union Health Minister Mansukh Mandaviya stated over 3.5 crore teens in the 15-18 age group had received the first dose of Covid-19 vaccines since Jan. 3. Two Covid-19 vaccines have the Indian government's approval for children (12+), Bharat Biotech's Covaxin and Zydus Cadila's ZyCoV-D.
Zydus VTEC manufactures the drug substance for the needle-free DNA Plasmid vaccine, ZyCoV-D. The manufacturing process and in-process material transfers within the plant are automated. Zydus has also entered into a definitive agreement with Shilpa Medicare Limited, a contract manufacturing organization, to produce mutually agreeable doses of ZyCoV-D. The Company also entered into an agreement with Enzychem Lifesciences of the Republic of Korea for the manufacturing license and technology transfer for the Plasmid DNA Vaccine.
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. The chemically synthesized Spike (S) gene region preceded by the 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. A miniprep plasmid isolation kit was cultured from each clone for plasmid isolation. 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 to prepare glycerol stocks and stored at −70 °C. In-vitro expression of DNA vaccine candidate was checked by transfection of the same in the Vero cell line.
DNA vaccines have been under development since the 1990s. The challenge for DNA vaccines is that they need to make it to the cell nucleus. As a result, DNA vaccines struggled to induce potent immune responses in clinical trials, so they were approved for use as vaccines only in animals.
On April 26, 2022, the DCGI authorized a two-dose regimen and will now be administered on days 0 and 28. Previously, it was approved as a triple dose on day 0, day 28, and day 56, for a total of 6 mg. A two-dose regimen for using a 3 mg dose was equivalent to the current three-dose regimen in a clinical trial. Previous clinical trials conducted dosage reviews.
ZyCoV-D Side Effects
A study published by The Lancet EClinical Medicine on July 16, 2021, found that most solicited AEs reported were after the first dose of vaccine, while the second and third doses of vaccination were well-tolerated. The ZyCoV-D Phase 1 safety data further suggests 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 essential aspect of the safety profile of SARS-CoV-2 vaccines. In addition, 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. Therefore, the ZyCoV-D vaccine is found to be safe, well-tolerated, and immunogenic in the Phase 1 trial.
ZyCoV-D is stored at 2-8 C 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.
Media reported in India that the vaccine costs 265 rupees ($3.53) per dose, and the applicator is offered at 93 rupees per dose, excluding GST.
ZyCoV-MV, COVID-19 Vaccine Candidate
Zydus Cadila has also developed a live, attenuated recombinant measles virus-vectored vaccine, ZyCoV-MV, to provide long-term immunity from COVID-19.
Zydus Cadila Financial News 2022
February 3, 2022 - Zydus announced for the third quarter ended December 31, 2021, Zydus reported consolidated revenues of Rs.3655 crores. Earnings before Interest, Depreciation, and Tax stood at Rs. 753 crores. Net Profit for the quarter stood at Rs. 500 crores.
ZyCoV-D COVID-19 Vaccine News 2021 - 2022
July 12, 2022 - Forbes India published: Gennova Biopharmaceuticals has become India's first mRNA Covid-19 vaccine maker.
June 7, 2022 - Chris Cappello, President, and CEO of PharmaJet, stated, "We congratulate our partner in the publication of their phase 3 clinical trial results in The Lancet and on their Emergency Use Authorization in India which further demonstrates the importance of the first DNA-plasmid vaccine for COVID."
April 1, 2022 - Zydus Lifesciences announced that safety and efficacy analysis data from the Phase III clinical trial of its Plasmid DNA COVID-19 vaccine ZyCoV-D has been peer-reviewed and published in The Lancet. The vaccine's efficacy stood at 66.6% at a time when the Delta Variant of the SARS COV-2 virus was the prevalent strain across India.
March 21, 2022 - ANI/Global Economic confirmed South Korea-based Hanmi Pharmaceutical would produce a plasmid DNA COVID-19 vaccine 'Zycov-D,' developed by India's Zydus Cadila, on consignment.
February 2, 2022 - Zydus Cadila started supplying its ZyCoV-D vaccine to the Government of India.
January 11, 2022 - Korean media reported Hanmi Pyeongtaek would begin producing the ZyCoV-D vaccine starting from the second quarter of 2022, aiming to manufacture up to 80 million doses per year.
January 4, 2022 - PharmaJet announced that its partner Zydus Cadila is partnering with Enzychem Lifesciences to manufacture their COVID-19 plasmid DNA vaccine (ZyCoV-D®) in Korea. The plan is to manufacture 80+ million doses of the ZyCoV-D vaccine.
November 26, 2021 - The media reported 2,37,530 doses of the ZyCoV-D vaccine had 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 would supply one 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 before 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 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 - India's local media reported that the ZyCoV-D vaccine would be made available to private sector hospitals.
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 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 ongoing.'
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 the 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.
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, 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 provides 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 permission 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 safe, well-tolerated, and immunogenic in Phase I/II clinical trials. The Company plans to initiate Phase III clinical trials with around 30,000 volunteers upon receiving the necessary approvals.
July 9, 2020 - COVID-19 Vaccine Development Update.
ZyCoV-D COVID-19 Vaccine Clinical Trials
Various clinical trials have been completed.
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 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. In addition, 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 was 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· nine 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. No deaths or serious adverse events were 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