Explainer: All you need to know about ZyCoV-D, the indigenous plasmid DNA COVID vaccine

Cadila Healthcare (Zydus Cadila) on August 20 received Emergency Use Authorization (EUA) from the Drug Controller General of India (DCGI) for ZyCoV-D, the world’s first and India’s indigenously developed DNA-based vaccine for COVID-19 to be administered in humans including children above 12 years of age and adults.

Earlier, the Subject Experts Committee (SEC) of the Central Drugs Standard Control Organisation (CDSCO) has recommended ZyCoV-D vaccine, clearing a major hurdle for the vaccine's emergency use.

ZyCoV-D is the world's first plasmid DNA COVID-19 vaccine to be approved and the second indigenous vaccine to be rolled out.

Here is an explainer on its safety, efficacy, delivery, and capacities.

Safety and efficacy

Zydus said ZyCoV-D exhibited a robust immunogenicity and tolerability and safety profile in the adaptive Phase I/II clinical trials. The three doses (2mg per dose) of the vaccine were found to have an efficacy of 66.6 percent for symptomatic RT-PCR positive cases in the interim analysis.

Zydus said it has found no severe cases on the COVID arm or deaths due to COVID-19 after the administration of the second dose of the vaccine. No moderate case of COVID-19 was observed in the vaccine arm, post the administration of the third dose, suggesting 100 percent efficacy in moderate cases.

A 'Covid arm' refers to a rash that may appear after receiving the vaccine. The Phase-3 clinical trials were conducted on over 28,000 volunteers 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 company said the study also shows that ZyCoV-D is safe for children in the age group of 12-18 years.

Needle-less vaccine
The vaccine is delivered through a needle-free applicator called the PharmaJet to ensure painless intradermal vaccine delivery. Moneycontrol learns that this device was developed in India in a record time.

Capacity

Zydus said it can produce 10-15 million doses of ZyCoV-D per month. The company said it can produce 3-5 crore vaccines by December. The capacity numbers suggest that Covishield and, to some extent, Covaxin will remain as the major workhorses for the government’s vaccination drive for some more time.

Evaluating two-dose regimen

Zydus said it has also submitted data for a two-dose regimen for ZyCoV-D, using a 3 mg dose per visit and the immunogenicity results had been found to be equivalent to the current three-dose regimen. The company said this would help in reducing the full-course duration of vaccination while maintaining a high safety profile in the future.

Children & adolescents

Zydus has submitted applications for EUA for children in the 12-18 year age group.

Novel approach

Zydus Cadila has taken a novel approach for its potential COVID-19 vaccine. Called plasmid DNA, the vaccine consists of genetic material of SARS-CoV-2 proteins, which instruct human cells to make the SARS-CoV2 antigen, eliciting an immune response.

The company says that this approach is easily replicable and scalable, requiring just Biosafety Level (BSL)-1. The vaccine can be stored at 2-8 degrees temperature, making it conducive for Indian cold-chain conditions. The vaccine is delivered through the intradermal route (between the layers of the skin), which makes its administration much easier. DNA vaccines are also theoretically easy to redesign quickly against a mutating virus.

Challenges

Firstly, the platform is novel. Not a single human vaccine using this platform has been approved anywhere in the world. The other big challenge is that the vaccine has to be administered in three doses – the first dose, and the other doses after 28 and 56 days.

Being a three-dose vaccine adds an additional layer of distribution and administration complexity, possibly raising the cost of the vaccine. While the company has promised to ensure that the vaccine is affordable, it has also sought approval for a two-dose vaccine.