How does the first covid-19 vaccine approved in the world work

India has just approved for emergency use the first human DNA vaccine against covid-19. Called ZyCoV-D, it has been developed by the company Zydus Cadila and is not only the first DNA vaccine designed to combat the disease, but also the first ever injection using this technology in humans. 

The first research carried out on this type of vaccine dates back to the early 1990s, but until now it had only been approved in animals, such as the injection against pancreatic disease in salmon, the one used against West Nile virus in horses, or the one against canine melanoma in dogs. 

The technology will now also be used in humans, after the Drug Controller General of India (DCGI) gave the green light for approval. The DNA vaccine is made up of small pieces of genetic material that, when inserted into plasmids – a small circular DNA molecule found in bacteria and other cells – will contain information on how the Spike protein, the antigen that will teach immune system cells to detect SARS-CoV-2, is produced. 

Unlike messenger RNA vaccines, such as Pfizer and Moderna, in which the mRNA was injected directly into the skin (and thus the genetic material did not need to access the nucleus of the cells first), DNA vaccines require this extra step, because it is there that it meets the messenger RNA, the 'scribe' that copies the information from the DNA and turns it into an instruction manual for protein production.

Advantages of DNA vaccines

In addition to the fact that it is much cheaper to produce than messenger RNA, DNA has a number of advantages over other vaccine types: firstly, it can be stored at more normal temperatures (between 2 and 8°C) than mRNA (between -60 and -80°C) because it is also a more stable genetic material. Moreover, according to the manufacturer, "it has shown good stability at temperatures of 25°C for at least three months'', which "will facilitate its transport and storage, and reduce any unexpected events related to cold chain breakage leading to vaccine wastage". 

The Indian vaccine does not require needles, but uses an intradermal injector. The developer company is Pharmajet, which states on its website that the contents are injected via a compressed beam that penetrates the subcutaneous area of the skin. Another feature that makes the Indian DNA vaccine different from others is that it is administered in 3 doses (like the Cuban Abdala vaccine), each 28 days apart from the previous one. The injection will be the first to be administered to minors in the country (from the age of 12).

Results of trials not yet published

What has not yet been made public are the results of efficacy in clinical trials. According to a press release from the manufacturer company, it is 67% effective against symptomatic infection, and 100% effective against moderate disease.

These percentages would have emerged after successful phase I/II and phase III clinical trials, the latter involving more than 28,000 volunteers, 1,000 of whom were between 12 and 18 years of age. The note also indicates that there were no serious cases or deaths from covid-19 after administration of the second dose of the vaccine. However, they have not yet been published in any scientific journal and therefore cannot be considered official. Nor is it known when they will start administering the vaccine. In the note, the date was set for September, without specifying the day. 

More DNA vaccines on the way

The Indian vaccine is the only one to be approved, but at least a dozen more are in development. Two, in fact, are already in advanced stages of research: that of the US-based Inovio Pharmaceuticals, based in Pennsylvania, and that of AnGes, based in Osaka (Japan). 

In addition to treating covid-19, the technology has already been proposed for use against other types of diseases, and long before the pandemic, such as allergies, some cancer types, virus respiratory syncytial virus, flu, and human papilloma.