Over ten months into the outbreak and spread of the novel coronavirus, the global race to develop a vaccine to contain its transmission is seeing frequent and rapid developments. Worldwide, there areclose to two hundredvaccine candidates at different stages of development. Most are in the pre-clinical stage while a few are in one of the three mandatory phases ofhuman clinical trials. In India, there are at least four candidates being developed, two of which have entered phase II trials.
India’s first indigenous Covid-19 vaccine, being developed by Bharat Biotech, is currently in the second phase of clinical trials, as is the candidate of Indian pharma company Zydus Cadila. Through partnerships, India has access to two other vaccine candidates in the country – AstraZeneca/Oxford’s viral vector vaccine and Novavax’s protein sub-unit vaccine.
ACCESS Health India is keeping a close track of the developments in the Indian context. Starting with this issue, we will present a monthly update on important candidates and their progress.
Dubbed as the “pharmacy of the world”, India is among countries with the largest capacity to produce COVID-19 vaccines. Its role in manufacturing a vaccine will be either mass producing one developed elsewhere or developing a new vaccine as well as manufacturing it. The possibility of the former is higher.
Developed by Swedish-British pharmaceutical firm AstraZeneca in partnership with Oxford University, the Covishield is among the most talked about vaccine candidates globally. In India, the Serum Institute of India in Pune is sponsoring its phase two and three human clinical trials. SII is the largest vaccine manufacturer in the world. It has been contracted by AstraZeneca and the University of Oxford to manufacture the vaccine for low and middle income countries.
The Covishield vaccine works on a mechanism that uses a weakened common cold chimpanzee virus to carry instructions to the body to make part of the SARS-CoV-2 virus. Once injected, the virus will infect a cell and tell it to make the spiky outer layer of the virus, known as the ‘spike protein’, the part of the virus that allows it to infect humans. The body’s immune system is expected to recognise this spike protein as a threat, and develop antibodies to fight it so that it will be ready to defend itself against the real virus.
SII has selected 18 sites in India to conduct the trial. Close to 1,600 candidates have taken part in the study. On August 3, the Drug Controller General of India permitted SII to conduct the second and third phases of human clinical trials of Covishield in the country.On August 25, SII began the second phase of trial.The trials ran into a roadblock and were halted following a show cause notice issued by the DGCI to the Pune firm over an adverse reaction that was detected in a volunteer at one of the global trial sites. This volunteer was reportedly enrolled in the UK arm of the trials, and had developed a serious spinal inflammatory syndrome called transverse myelitis. After the UK authorities declared the vaccine shot safe on September 12, DGCI gave its go ahead to SII on September 15 to resume trials in India. Phase three trials began at the JSS Academy of Higher Education and Research (JSSAHER) in Mysuru on September 29 with 120 volunteers.
Covaxin is the first indigenouslydeveloped vaccine against Covid-19. Indian pharma company Bharat Biotech is collaborating with the Indian Council for Medical Research and the National Institute of Virology for its development. It is an inactivated vaccine candidate, designed to produce unique elements of the SARS-CoV-2 virus, which are used by the immune system to recognize a threat if the whole virus in ever encountered in the real world.The study is intended to assess the safety, reactogenicity, tolerability and immunogenicity of the whole-virion inactivated Covid-19 vaccine in healthy participants.
In June this year, Bharat Biotech secured approval from the Drug Controller General of India (DCGI) to conduct clinical trials of Covaxin, Trials began on July 15 across 12 medical institutes in the country.
Covaxin received the regulatory approval to advance into Phase II clinical trials from September 7. The DCGI granted approval for Phase III of the trials on October 23. The trial will test the safety and efficacy of the shot, and will reportedly be conducted in about 25,000-30,000 volunteers.
Bharat Biotech recently shared the results of their COVID-19 vaccine candidate safety trials in animals. The experimental shot, called ‘COVAXIN’, was found safe in rhesus monkeys that were vaccinated and exposed to the SARS-CoV-2. The results from the preliminary trial suggest that the vaccine is safe, according to principal investigators conducting the trials.
The India trials of a vaccine candidate being developed by American company Novavax is likely to begin in late October. The Novavax vaccine candidate is currently undergoing phase-2 clinical trials in South Africa. Global phase-3 trials are expected to begin next month. In India, Novavax has entered into an agreement with Pune-based Serum Institute of India for production of 100 million doses of the vaccine. It is expected that at least 50 per cent of this would be meant for supplies within India.
The NVX‑CoV2373 vaccine is engineered from the genetic sequence of SARS‑CoV‑2, the virus that causes COVID-19 disease. NVX‑CoV2373 was created using Novavax’ recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and contains Novavax’ patented saponin-based Matrix-M™ adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies.
In preclinical trials, NVX‑CoV2373 demonstrated indication of antibodies that block binding of spike protein to receptors targeted by the virus, a critical aspect for effective vaccine protection. Novavax has secured $2 billion in funding for its global coronavirus vaccine program, including up to $388 million in funding from the Coalition for Epidemic Preparedness Innovations (CEPI).
Another vaccine is being developed by Zydus Cadila. Dubbed as ZyCoV-D, Zydus’ COVID-19 vaccine commenced phase II clinical trials from August 6. ZyCoV-D was found to be safe and well tolerated in the phase I clinical trial. Phase III trials are likely to begin soon.
Another Indian pharma company, Hyderabad based Biological E (BE), has agreed to manufacture the vaccine candidate of Johnson & Johnson’s subsidiary, Janssen Pharmaceutica NV.
Meanwhile, Dr Reddy’s Laboratories has received permission for conducting phase II clinical trials of the Russian COVID-19 vaccine Sputnik V in India. It is developed by the Gamaleya Research Institute and the Russian defence ministry. Dr Reddy’s said that phase II trial would include 100 subjects, while the phase III would involve 1,400 volunteers.
Why is vaccination the ultimate solution?
The Covid-19 virus needs the spike protein to attach to and enter human cells to reproduce. Researchers have shown that antibodies, like those made by the human immune system, bind to the spike protein, neutralize it and prevent the coronavirus from infecting cells in laboratory culture.Vaccines in clinical trials have been shown to raise anti-spike antibodies that block virus infection in cells in the lab.
Phase I and phase II trials test if a vaccine is safe and induces an immune response. Results from ongoing vaccine trials show triggering the production of anti-spike neutralizing antibodies levels that are two- to four-fold higher than those seen in people who have recovered from COVID-19.
During a phase III trial, the final step in vaccine development process, the vaccine is tested on tens of thousands of individuals to determine if it works to prevent infection with SARS-CoV-2, and that it is safe.
How soon can we get the vaccine?
Research agency Bernstein said in a report that an approved vaccine is likely to hit the Indian market by the first quarter of 2021. “Phase I/II data looks promising for both in terms of safety and the vaccine’s ability to elicit an immune response,” it said. “We are optimistic that there will be an approved vaccine in the market by 1Q calendar year 2021 in India,” the report stated.
Despite India’s success in mass manufacturing, the transition to innovation and new product development has been a struggle. Nevertheless the Serum Institute, Aurobindo Pharma, Bharat Biotech, BE, Indian Immunologicals, Mynvax, Panacea Biotech and Zydus Cadila are all attempting to develop their own vaccines.
Thanks to its vast manufacturing capacity, India will, without a doubt, export vaccines. Vinod Paul, chair of India’s National COVID-19 Task Force said, “The vaccine is not just for India and Indians but for the world and humanity.” The question is when. Many in low and middle-income countries will undoubtedly be hoping it will be sooner rather than later.