The world’s first DNA vaccine against Covid-19 is all set for launch in India. The three-dose ZyCoV-D shot developed by the Ahmedabad-based Zydus Cadila is also unique because it uses a needle-free injector that shoots the vaccine under the skin as a high-pressure jet. It is also the first India-made vaccine that can be administered to the 12-17 years age group.
What Makes ZyCoV-D Different?
ZyCoV-D received its emergency nod from the Drug Controller General of India (DCGI) on August 20 this year, becoming the country’s second homegrown vaccine after Bharat Biotech’s Covaxin. Referring to the tech behind the vaccine, the company said that “this is for the first time that a technologically advanced vaccine has been successfully developed on the Plasmid DNA platform for human use".
It is also India’s first vaccine that can be administered to children after it was trialled on the 12-17 years age group. Reports said that a chunk of this vaccine could be earmarked for children with the initial doses likely to go to those with underlying health conditions that make them vulnerable to Covid-19.
Zydus Cadila has also highlighted the “rapid plug and play technology" of ZyCoV-D as something that allows the vaccine to “be easily adapted to deal with mutations in the virus".
A report in the journal ‘Nature’ says that though scientists have long pursued vaccines based on the DNA platform, a drawback has been the immune response they have been found to elicit. It notes that “despite being more potent than previous DNA vaccines", ZyCoV-D is a three-dose vaccine as against the two-dose primary regimen that is common to most of the prominent Covid-19 vaccines being used at present, although booster shots are now being lined up by most pharma majors.
With an eye on securing a better immune response, ZyCoV-D has also adopted a delivery mechanism that is unlike anything used by the major Covid-19 vaccines: rather than being injected into the muscle, the vaccine is going to be pumped under the skin “using a needle-free device… which creates a fine, high-pressure stream of fluid that punctures the surface and is less painful than an injection".
How Will The Vaccine Be Administered Without An Injection?
ZyCoV-D is an ‘intradermal vaccine’ that is applied using a “needle-free system" that the company says “can also
lead to a significant reduction in any kind of side effects" apart from representing a great benefit for those who may be jittery about getting vaccinated due to a fear of needles.
The US-based PharmaJet, whose Tropis needle-free injector will be used for vaccination with ZyCoV-D, says that the device creates a “narrow, precise fluid stream that delivers the medicine or vaccine into the skin". While the needle-free technology itself has been around since the 1940s, the company says it has undergone innovations to evolve into “a safe and effective method of administration". The needle-free mechanism helps avoid “needlestick injuries" and also provides an environmental benefit as it saves on the use of disposable syringes.
What Is The Vaccine’s Efficacy Rate?
Preliminary results from Phase-III clinical trials showed it had a 66.6 per cent efficacy rate against the novel coronavirus. The New York Times said the company announced that “none of the vaccinated volunteers in the trial developed severe disease or died, making ZyCoV-D the first DNA-based vaccine shown to work against Covid-19".
The Phase-III trials were conducted at 50 sites across the country and involved over 28,000 volunteers, the company said, adding that with the trial having been conducted during the peak of the second wave of Covid-19 in the country, it was confident about “the vaccine’s efficacy against the new mutant strains especially the Delta variant".
While ZyCoV-D’s efficacy rate in trials is substantially lower than that of other nucleic acid vaccines, like the ones produced by Pfizer-BioNTech and Moderna, experts point out that those vaccines had been trialled at a time when earlier, less transmissible, variants were circulating whereas the ZyCoV-D trial was held after the more infectious Delta variant had emerged.
The company, which sought emergency approval for ZyCoV-D from the Indian drugs regulator in July based on the preliminary Phase-III results, is yet to release late stage results of the trials. Publication of its findings in a peer-reviewed journal is also awaited. Dr Sharvil Patel, managing director of Zydus Group, had told News18.com in early September that the Phase-III clinical trial was ongoing and that they are “preparing the manuscript based on the interim analysis and shall be submitting the same for publication to a reputed journal shortly".
So, What Kind Of Vaccine Is ZyCoV-D?
The Zydus Cadila shot belongs to a category known as genetic or nucleic acid vaccines. These vaccines work by inserting a piece of the virus’s genetic information into the body to prompt cells to produce a key component of the virus — namely, its spike protein that the novel coronavirus uses to invade and latch on to human cells. The immune system recognises and attacks this spike protein by producing antibodies. Genetic vaccines can be based both on RNA — like the Pfizer and Moderna mRNA shots being used in the US — or DNA.
According to US-bases think tank Milken Institute, “DNA-based vaccines work by inserting a genetically engineered blueprint of viral gene(s) into small DNA molecules (called plasmids) for injection into vaccinated people". Once inside the human body the “cells take in the DNA plasmids and follow their instructions to build viral proteins, which the immune system recognises as foreign, triggering the immune response that protects against the disease".
While they have become the frontline vaccine against the novel coronavirus in many countries across the world, the pandemic marks the first instance of the rollout of genetic vaccines for human use. Gavi, a public–private global health partnership working on vaccine access for poorer countries, says that “several DNA vaccines are licensed for animal use, including a horse vaccine against West Nile virus".
What About Dosage, Storage And Delivery?
In a world of mostly two-dose Covid-19 vaccines (and the rare single dose shot like the one made by Johnson and Johnson), ZyCoV-D is, interestingly, a three-dose shot with NYT saying it is delivered four weeks apart. But the company has said that it has “also evaluated a two dose regimen for ZyCoV-D vaccine using a 3mg dose per visit and the immunogenicity results had been found to be equivalent to the current three dose regimen".
As to the logistics, the vaccine can be stored at 2-8 degrees Celsius temperatures but the company adds that it “has shown good stability at temperatures of 25 degrees Celsius for at least three months". That would enable easy transportation and storage, unlike mRNA vaccines, which require ultra-cold storage.
The company said in a release annoucing the emergency nod for ZyCoV-D that it plans to manufacture 10-12 crore doses annually of the vaccine.
How Safe Are Genetic Vaccines? How Tough Is To Produce These?
These vaccines are considered to carry no risk of causing an actual infection as they use no live components of the virus but just some genetic information encoded by it.
As to production, once the virus’s genome is sequenced, it can be quite readily produced. Gavi says that “Moderna’s RNA vaccine against Covid-19 entered clinical trials within two months of the SARS-CoV-2 genome being sequenced". Zydus Cadila has stated that the plasmid DNA platform “provides ease of manufacturing with minimal biosafety requirements" and is also easily adaptable to target any future mutations.
Apart from Zydus Cadila, a handful of other makers across the world are exploring DNA vaccines, including Japanese biotechnology company AnGes, which has Osaka University among its partners, and the US-based Inovio.