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Explained: How does Zydus Cadila’s ‘plasmid DNA’ vaccine work?

The science behind the ZyCoV-D vaccine

The ZyCoV-D vaccine | Zydus Cadila

Vaccine development used to span between 10-15 years, but with the urgency brought about by the COVID-19 pandemic, vaccines against the SARS-CoV-2 virus have been made in just over a year.

The different types of vaccines that have been deployed so far include mRNA (messenger ribonucleic acid), adenoviral vectors, inactivated virus, recombinant and peptide antigen, among others. Now, Gujarat-based Zydus Cadila’s ZyCoV-D vaccine is the latest to be sought emergency use approval for, with Zydus approaching the Drug Controller General of India (DCGI) for the same on July 1.

ZyCoV-D is the first vaccine in the fight against COVID-19 to be DNA plasmid based.

The first vaccines to be approved worldwide in the fight against COVID-19 made use of messenger RNA—which contain coded instructions for cells to make the spike proteins from the coronavirus that are necessary to trigger an immune response against the coronavirus.

DNA vaccines work on a similar principle, using DNA extracted from bacteria to teach cells to create proteins that can trigger an immune response. However, in ZyCoV-D’s case, the plasmids—a type of DNA found mostly in bacteria—are used to convey the instructions. These vaccines prove more versatile and easier to store at higher temperatures (Zydus Cadila’s chairman had said that the vaccine was stable not just at 2-8 degrees celsius but also at even 30-degree temperatures for about three months).

Another aspect that makes the ZyCoV-D vaccine unique is that it can be administered intradermally without an injection, instead using a fluid jet that penetrates the skin—which the company says is painless and could reduce side effects from the jab. The company says it uses the “PharmaJet” needle-free system Tropis. PharmaJet, a Colorado-based company, says its is a “single-use, sterile, disposable syringe used with a reusable injector”. The advantages are reduced injuries from needles and reduced waste generated since there is no needle in the process.

Combined with the delivery system as well as the nature of DNA viruses itself (the company says it can be manufactured at a BSL-1 grade lab), Zaydus Cadila’s vaccine candidate is likely to be very cost-effective.

It is also administered in three doses.

Dr. Sharvil Patel, Managing Director, Cadila Healthcare Ltd., said, “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.”

The company said it has also evaluated a two dose regimen for ZyCoV-D vaccine using a 3 mg dose per visit and the immunogenicity results had been found to be equivalent to the current three dose regimen.

How did the virus perform in interim trials?

Primary efficacy of 66.6 per cent has been attained for symptomatic RT-PCR positive cases in the interim analysis, the company said, citing interim results from Phase III clinical trials with over 28,000 volunteers in over 50 clinical sites across India. The trial was held during the peak of the second wave of COVID-19, the company said.

No moderate case of COVID-19 disease was observed post administration of the third dose, suggesting 100 per cent efficacy against moderate disease, Zydus Cadila said.

No severe cases or deaths due to COVID-19 occurred after administration of the second dose of the vaccine.

The company has also evaluated a two-dose regimen for ZyCoV-D vaccine using a 3 mg dose per visit and the immunogenicity results had been found to be equivalent to the current three-dose regimen, Zydus Cadila said.

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.

With inputs from PTI