In a move that will accelerate the pace of vaccinations in the country, India recently approved a new homegrown vaccine against COVID-19. The vaccine is the world’s first plasmid DNA vaccine. Developed by the Indian pharmaceutical company Zydus Cadila, the new COVID vaccine uses strands of DNA to prime the immune system against the SARS-CoV-2 virus. It will also be the first vaccine in India to be administered to children (above 12 years of age). 

The three-dose ZyCoV-D vaccine is administered into the skin without an injection. It has been found to have an efficacy of 66 percent in protecting against symptomatic COVID-19 infection in clinical trials that involved more than 28,000 participants. ZyCoV-D will be administered on day zero, day 28, and the final dose on the 56th day. It is likely to start being administered in India from October and the company plans to produce up to 50 million doses by early next year. Despite the efficacy not being particularly high compared to other COVID-19 vaccines, ZyCoV-D being a DNA vaccine is a significant factor from the point of view of vaccine research and development.[1]

According to Zydus Cadila, the vaccine was tested in about a thousand people belonging to the 12-18 age group and the jab was found to be “safe and very well tolerated” in this age group. Bharat Biotech’s Covaxin and ZyCoV-D are the only two vaccine candidates to have been tested among children in India. They are also the only ones to be developed indigenously. ZyCoV-D has been developed in collaboration with the Department of Biotechnology, Government of India, the National Institute of Virology, and the Indian Council of Medical Research. 

So what does it mean to be the world’s first DNA-based vaccine to be administered to humans? The research community sees the approval of ZyCoV-D as an important step forward in the global fight against COVID-19 as it shows that we have another class of vaccines that can be put to use. The ZyCoV-D vaccine also ushers in a wave of DNA vaccines for various other diseases that are currently in different stages of development across different parts of the world. Around eleven DNA vaccines against COVID-19 are in clinical trials globally, and more are in earlier stages of development.[2] Previous DNA vaccines have worked well in animals but not humans.[3]

Researchers are upbeat about this development because of a general consensus that that potential success of DNA vaccines can be a big boost to the future of vaccine science as they are easy to manufacture and are more stable than mRNA vaccines, which are known to require storage at very low temperatures.

How does the ZyCoV-D work? 

WHO describes DNA vaccines as a radically new approach to vaccination. [4]. ZyCoV-D contains circular strands of DNA known as plasmids, which encodes the spike protein of the SARS-CoV-2 virus. Once the plasmids enter the nuclei of cells, they are converted into mRNA, which travels to the main body of the cell and is translated into the spike protein itself. The body’s immune system then mounts a response against the protein, and produces tailored immune cells that can fight future infections.[5].

DNA vaccines can potentially offer many advantages over traditional approaches, including better stimulation of cell responses, improved vaccine stability at higher temperatures, and the relative ease of large-scale manufacture making them relatively cheaper. ZyCov-D is also India’s first needle-free Covid-19 vaccine, administered with a disposable needle-free injector, which penetrates the skin and delivers the jab to the proper tissue. The Department of Biotechnology said that the “plug-and-play” technology on which the plasmid DNA platform is based can be easily adapted to deal with mutations in the virus. [6]

However, DNA vaccines developed for infectious diseases in humans have known to have little success in the past. They work well in animals but are not known to offer the same level of immune response in humans because of the difficulty in pushing plasmid DNA into the nucleus of human cells.[7]. The other potential drawback is that ZyCoV-D requires three doses, instead of two for the other two candidates being used in India. Zydus Cadila recently said that it is evaluating a two-dose jab.

Fatality rate falls amid persistent daily positive cases 

COVID-19 numbers reported from the country continue to show mixed patterns, even as the vital R value, or the reproductive rate of the virus continues to hover over 1.  While the number of new infections continue to be at moderate levels, it is their consistency over the past three months that remains to be a cause of worry.  R value denotes the number of people an infected person will pass on the virus to. In times of a pandemic, public health authorities target an ‘R’ value of less than 1. If the R value is higher than one, then the number of cases keeps increasing.[8] When the R number is lowered to below 1, the disease will eventually stop spreading. 

Even as less than 50,000 daily new cases are being reported for over 70 consecutive days, the numbers are nowhere close to the lowest recorded single day new cases in 2021 which was on February 1 when 8635 new cases were reported. 

On September 6, the number of people succumbing to COVID-19 during a span of 24 hours was lowest since March, at 219 deaths. India had reported 199 deaths in a single day on March 23. However, even as the case positivity rate continues to be below 3 percent for the last 72 days, it has risen from 1.9 percent on August 23 to 2.6 percent on September 6. 

With 38,948 new coronavirus cases  and 43,903 recovered cases on Sep 06 2021, India now has registered a total of 3,30,27,621 COVID-19 infections across the country. This includes 219 new deaths which have taken the total count to 4,40,752. The total number of coronavirus cases also includes 3,21,81,995 people who have recovered and 4,04,874 who are currently being treated. The national COVID-19 recovery rate was recorded at 97.44 per cent. The case fatality rate has declined to 1.33 per cent, according to MoHFW data. 

In terms of daily caseloads, Kerala Maharashtra, Andhra Pradesh, and Mizoram are showing a continued surge. These are the same states that have an R-factor value of more than 1. Kerala accounts for a maximum number of active cases at present at nearly 70 per cent of the new infections and a third of deaths. 

Vaccination pace continues to improve

The improving pace of vaccination in the country presents hope in bringing the pandemic under control. According to the Health Ministry, a total of 68.75 crore doses of Covid-19 vaccines have been administered across the country as of September 5. About 52.63 crore Indians have received the first dose, while 16.11 crore Indians have been fully vaccinated as on September 5. 

As per MoHFW data, over 18 crore jabs were administered in August. This was more doses than all the Group of Seven (G7) countries – Canada, the UK, the US, Italy, Germany, France and Japan – put together, according to an official statement [9]. India gave six million jabs on an average every day in August, compared to 4.3 million daily jabs in July, according to official data. More than half of India’s eligible population have received at least one dose of the Covid vaccine,  as per official data. However, only about 17 percent of eligible adults have been fully vaccinated since the beginning of the drive in January. Regional differences also persist in the vaccination coverage. 

Despite the increased pace, the vaccination drive needs to pick up further. India currently ranks 14th among 30 populous countries with regard to COVID-19 vaccine doses per 100 people [10]. In terms of percentage of fully vaccinated population, India ranks 17 among these 30 countries. India will need to administer an average of 10 million doses a day if it is to meet the year-end target of fully vaccinating the estimated population of 94 crores of those aged 18 and above (2021 Census office estimate). 

Supply constraints and vaccine hesitancy that have been behind slow vaccination rates in the past months are likely to become less of factors in the months ahead. The government has stated that it expects increased supplies from all vaccine manufacturers in the weeks to come.

Conclusion 

Vaccination coverage has seen notable improvement in the recent weeks. As more than two-thirds of Indians already have Covid-fighting antibodies, mainly through natural infection, experts think that with a well-managed and sustained vaccination program, the next surge in cases is likely to be less deadly than the second wave. 

The government, nevertheless, has warned that like in Kerala, the rest of India could also see a rise in infections around the festival season starting this month and ending in early November. Some parents are also worried about a possible surge in infections with the voluntary reopening of physical classes for school students in some states. With a significant proportion the population still unvaccinated, it is not safe to assume that India is immune from the possibility of future waves. India cannot afford to be complacent on any front- be it containment measures, genomic surveillance, COVID appropriate behaviour or the sustained and accelerated vaccination program. 

 [1] https://www.nature.com/articles/d41586-021-02385-x

[2] https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines

[3] https://www.bbc.com/news/world-asia-india-57774294   [2]

[4] https://www.who.int/teams/health-product-policy-and-standards/standards-and-specifications/vaccines-quality/dna

[5] https://www.nature.com/articles/d41586-021-02385-x

[6] https://www.hindustantimes.com/india-news/zydus-cadila-s-covid-vaccine-for-children-over-12-approved-10-points-101629520295788.html

[7] https://www.bbc.com/news/world-asia-india-57774294

[8] https://www.bbc.com/news/health-52473523

[9] https://www.bbc.com/news/world-asia-india-56345591

[10] https://www.news18.com/news/india/india-covid-vaccinations-august-higher-than-g7-combined-4167917.html

Photo Credits: Tribune India