Recently, India approved the world’s first new DNA crown vaccine for human vaccination – zycov-d. The vaccine uses a circular DNA strand to activate the human immune system against the invasion of sars-cov-2 virus. The clinical trial results showed that the protective rate of the vaccine for symptomatic COVID-19 pneumonia was 67%. The vaccine was approved for use in India in September for people aged 12 and over.
The researchers said that although the efficacy of the vaccine may not be the highest, its significance as the first DNA vaccine is self-evident. For a long time, the project of DNA vaccine research has been ongoing, and many other DNA vaccines may be available soon after. The approval of zycov-d indicates that the upsurge of DNA vaccine against various diseases may be coming.
“If DNA vaccines prove successful, this is the future of vaccinology,” said Shahid Jameel, a virologist at Ashoka University in India
The urgency of fighting COVID-19 has accelerated the pace of research and development of the use of gene vaccine, such as RNA vaccine and DNA vaccine. In clinical trials, RNA vaccine has been proved to be able to establish a strong immune response in vivo, and has been widely used in many countries. However, mRNA vaccines usually need to be stored at very low temperatures. In this regard, the advantage of DNA vaccine is that the preservation is more stable, and the production process is also simple, which is conducive to large-scale production and transportation.
The ZyCoV-D vaccine was developed by Zydus Cadila, a pharmaceutical company based in Ahmedabad, India. It contains a cyclic DNA chain known as plasmid (encoding COVID-19 spike protein) and a promoter sequence that activates the spike protein gene. After the plasmid enters the nucleus, it will be transformed into mRNA, which then enters the cell body (cytoplasm) and translates itself into spike protein. Subsequently, the body’s immune system mobilizes the immune response to spike proteins to produce customized immune cells that can eliminate future infections. Plasmids generally degrade within weeks and months, but the immune effect will be maintained.
The results showed that the vaccine had 67% protective effect. This data comes from a clinical trial of 28000 subjects. Among them, 21 cases of symptomatic infection occurred in the vaccine group; There were 60 symptomatic infections in the placebo group.
The research and development history of DNA vaccine and mRNA vaccine can be traced back to the 1990s. Jameel believes that the challenge of DNA vaccines is that they need to go directly to the nucleus, while mRNA only needs to reach the cytoplasm. Therefore, for a long time, DNA vaccine can not induce strong immune response in clinical trials.
To solve this problem, the inoculation of zycov-d vaccine uses a needle free syringe to press on the skin. The high-pressure liquid flow penetrates the skin surface and is delivered under the skin rather than deep in the muscle tissue. There are a large number of immune cells in the area under the skin that can phagocytize and dispose of foreign virus particles. DNA capture here is much more efficient than muscle and less painful than injection.
Zycov-d vaccine also has disadvantages. For example, it takes at least three injections to achieve its initial efficacy, which puts pressure on vaccine transportation. In addition, other researchers have questioned the vaccine. On the one hand, its effectiveness is not as good as that of some existing mRNA vaccines, and the effectiveness of the latter can reach more than 90%. In this regard, jammel believes that the data of zycov-d vaccine are aimed at Delta mutants with stronger transmission power, while the data of mRNA vaccine are aimed at primary viruses, so it can not be simply compared from the data.
In addition, some researchers believe that the approval process of the vaccine is not transparent enough because the data at the later stage of clinical trials have not been published. Zydus Cadila said that the clinical trial is not over and will publish the complete analysis results soon. The company also said that the vaccine will be given priority in India in September and is expected to produce 50 million doses by the beginning of next year.
Prospect of DNA vaccine
Currently, many COVID-19 DNA vaccines are being developed worldwide. They use different antigens and transmission mechanisms. Among them, two vaccines have reached the late stage of clinical trial: one is the vaccine of angles company in Osaka, Japan; The other is the vaccine developed by inovio pharmaceutical company, which is assisted by Weiner. Among them, inovio vaccine needs to be injected subcutaneously. The delivery device used by inovio vaccine sends a short electric pulse to the skin and forms small holes in the cells to let the vaccine enter.
DNA vaccine in clinical trials
According to the vaccine tracking data of the World Health Organization in the above table, some new coronal DNA vaccines are in the early stage of clinical trials. One of them was developed by geneone life science, a biotechnology company in Seoul, Korea. The other is developed by bionet company in Bangkok, Thailand, and is currently conducting phase 1 clinical trial in Australia.
Not just for COVID-19, more DNA vaccines are being developed for diseases that are currently not available for vaccines, such as cytomegalovirus that can pass to the fetus during pregnancy, and respiratory syncytial virus infection. In addition, DNA vaccines against influenza, human papillomavirus (HPV), HIV (HIV), and Chai virus are also being developed. Even anti-cancer vaccines are expected to become possible.