April 1 The clinical trial outcomes of the world's first plasmid DNA vaccine - ZyCoV-D - have been peer reviewed and published in medical journal, The Lancet. The study findings state that the vaccine is "efficacious, safe and immunogenic".
The developer, Zydus Lifesciences Ltd (formerly Cadila Healthcare Limited), is said to be gradually rolling out its three-dose vaccine for mass inoculation. The outcomes of the Phase I/II clinical trials were earlier published in the EClinical Medicine Journal of The Lancet.
Of the 33,194 individuals screened between January 16 and June 23, 2021 (data cutoff), 5,241 did not meet screening criteria and 27,703 were enrolled and randomly assigned to receive ZyCoV-D (n=13,851) or placebo (n=13,852). Per-protocol, 81 cases were eligible and included in efficacy analysis.
The article notes that the study provides "the first evidence that induction of immune responses against the spike protein using a plasmid construct carrying the spike-S-gene, provides protection against Covid-19."
The "three-dose regimen of ZyCoV-D, administered intradermally via a needle-free injection system, was found to be 66.6 per cent effective against COVID-19."
The plasmid DNA platform also allows for the rapid generation of new constructs to deal with mutations in the virus.
The article states, "The three-dose regimen that might be perceived as cumbersome, is actually equivalent to a third booster dose, which is being considered by many countries in existing vaccine platforms." ZyCoV-D is administered at an interval of 0-28-56 days, with a combined vaccine dosage of six milligram (6mg).
Managing Director, Zydus Lifesciences Ltd, Sharvil Patel, said, "We are pleased that the outcomes of the Phase III trial have been peer reviewed and published in The Lancet. This attests to compliance with global best practices and stringent peer review parameters of clinical trials."
The Lancet also recognised the use of a needle-free injection system for vaccine administration, which "should result in a reduction of side-effects typically associated with needle use (eg, injection site pain)." ZyCoV-D is stored at 2–8°C, but is stable at 25°C for at least 3 months, retaining all the specifications set by the US Food and Drug Administration and other international guidelines.
"Thermostability will aid transportation and storage of the vaccine and reduce any cold chain breakdown challenges, thereby preventing vaccine wastage," the study noted.
Also, the plasmid DNA platform provides ease of manufacturing with minimal biosafety requirements. Being a plasmid DNA vaccine, ZyCoV-D does not share the problems often associated with vector-based immunity, such as poor immune response to target antigens following vaccination due to pre-existing antibody titres to vectors resulting from natural infections from vectors such as adenoviruses, measles, and influenza viruses.
The double blind, placebo controlled, randomised Phase III clinical trial was one of the largest trials for a Covid-19 vaccine in India and was conducted on over 28,000 healthy adult volunteers in over 50 sites across the country.
It was supported by a grant-in-aid from 'Mission Covid Suraksha' under the National Biopharma Mission, Department of Biotechnology.