COVID-19: Zydus Cadila’s DNA vaccine shows 100% efficacy in teens

Indian Pharmaceutical major Zydus Cadila has become the world’s first to seek approval for a DNA-based vaccine against COVID-19, with trials indicating 100% efficacy in adolescents against moderate disease after three doses.

The vaccine, which is likely to be approved by Indian authorities, also promises relief for those afraid of needles, as it can be delivered using a new, needleless injection technology known as Pharmajet. The technology uses a narrow stream of fluid to penetrate the human skin and deliver the vaccine subcutaneously.

More importantly, ZyCoV-D has is likely to become the second vaccine to be developed entirely in India. The first one was Covaxin, which was developed by researchers from Bharat Biotech and Indian Council of Medical Research.

What makes ZyCoV-D different is that it uses DNA technology, and may become the first widely used vaccine in the world to work on this principle.

DNA vaccines work by modifying the DNA inside the human cell. Due to this modification, the human cell starts producing a particular chemical or protein, and this protein leads to an immune reaction in the body. In this case, the human cell starts producing the spike protein of the COVID-19 virus.

This leads to an immune reaction in the body, which generates antibodies that are useful in neutralizing any attack by the virus later on, giving the person immunity to the virus.

The most widely used COVID-19 vaccines in the US, Pfizer and Moderna, are also based on a similar technology. However, unlike ZyCoV, these vaccines use RNA to induce the human cell to make the virus’ spike protein and lead to an immune reaction.

A US Govt graphic showing how mRNA vaccines work

RNA is also a ‘life chemical’ in that it too contains the code for making proteins. But RNA is located outside the cell nucleus (or the core of the cell) and in certain cellular structures called mitochondria, which are supposed to be remnants of bacteria-like organisms that ended up becoming part of the human cell.

DNA, on the other hand, is kept inside the core of the human cell to protect it from being modified by chemicals that come into the cell, such as chemicals from food and the air. This is because damage to DNA can result in diseases like cancer and genetic mutation in offspring, while damage to RNA may result in less long-term symptoms such as a lack of energy.

Because of the highly protected and sensitive nature of DNA, it has been considered more challenging to try to use DNA vaccines to produce the required chemicals. However, some DNA vaccines have been tried out for animal vaccination.

DNA vaccines are easier to store as DNA does not disintegrate at regular refrigerator temperatures, while RNA requires deep freeze facilities that have to be custom built for the purpose. This is the primary reason why RNA vaccines like that of Pfizer and Moderna have not become popular in countries like India.


Zydus Cadila said its DNA vaccine was tested in 28,000 people as part of its Phase III clinical trial, making it the largest such test for any COVID-19 vaccine in India.

The company said the results of the vaccine were impressive in the 12-18 group — a segment that is yet to be vaccinated in India.

“This was..the first time that any COVID-19 vaccine has been tested in adolescent population in the 12-18 years age group in India. Around 1000 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. Whereas, 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. No severe cases or deaths due to COVID-19 occurred in the vaccine arm after administration of the second dose of the vaccine,” it said.

Sharvil Patel, MD of Cadila Healthcare, said the vaccine has proven its safety despite being the first every plasmid DNA vaccine for human use.

“This breakthrough marks a key milestone in scientific innovation and advancement in technology. As the first ever plasmid DNA vaccine for human use, ZyCoV-D has proven its safety and efficacy profile in our fight against COVID-19. The vaccine when approved will help not only adults but also adolescents in the 12 to 18 years age group.

“This has been possible because of the collective support of the Government, the regulators, the volunteers who had faith in the process, the investigators who conducted the multi-centric trials all through these months, the suppliers who worked closely with us and our dedicated team of researchers and vaccine professionals who worked tirelessly on the vaccine and also manufactured the trial doses,” he said.

The Company has also evaluated a two-dose regimen for ZyCoV-D vaccine using a higher dose (3 mg) per visit and the immunogenicity results had been found to be equivalent to the current three dose regimen. “This will further help in reducing the full course duration of vaccination while maintaining the high safety profile of the vaccine in the future,” it added.

ZyCoV-D is stored at 2-8 degree Celcius temperature, but the company said it has shown good stability at temperatures of 25 degrees 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 vaccine wastage. The plasmid DNA platform provides ease of manufacturing with minimal biosafety requirements (BSL-1),” the company said.

Zydus Cadila has wide range of capabilities in developing and manufacturing vaccines. It was the first company in India to develop and indigenously manufacture the vaccine to combat Swine Flu during the pandemic in 2010.

It has also indigenously developed numerous vaccines successfully including tetravalent seasonal influenza vaccine (first company in India to indigenously develop and commercialize), Inactivated Rabies vaccine (WHO Prequalified), Varicella vaccine (first Indian company to indigenously develop and receive market authorization), Measles containing vaccines (MR, MMR, Measles), Typhoid conjugate vaccine and pentavalent vaccine.

The company is also working on Measles-Mumps-RubellaVaricella (MMRV), Human papillomavirus vaccine, Hepatitis A, Hepatitis E vaccines.