Is the dire need for a cure against the pandemic propelling us to ignore ironclad medical norms at our peril?
There is a global race against time to find an appropriate vaccine against the coronavirus. While the urgency is well appreciated, there is no way a vaccine for such a deadly virus can be fast-tracked without going through the established and time-proven protocols.
Vaccine trials can be broadly defined into three phases: phase 1 focuses on the safety of the vaccine on a small group of respondents; phase 2 tests the efficacy, determining the required dosage for an effective immune response; and phase 3 puts the vaccine to the test on a larger scale, across age and population groups.
Generally, after pre-clinical studies, the first phase itself takes around six to 18 months. Once proved to be safe and successful, licences are issued for commercial release.
WHO reported in the second week of July that there are 23 candidate vaccines in clinical evaluation and 137 candidate vaccines in pre-clinical evaluation. Eleven of the 23 are currently undergoing human trials, including two Indian vaccines. The top promising contenders so far, and looking to start human trials, are:
- Sinovac (Sinovac Biotech Ltd. in China) based on a SARS platform. Sinovac says its inactivated vaccine protected monkeys against the virus, using weakened forms of the COVID-19 virus.
- ChAdOx1-S (University of Oxford/AstraZeneca in the U.K.) based on influenza.
- Adenovirus Type 5 Vector (CanSino Biological Inc./Beijing Institute of Biotechnology in China) based on the Ebola research. It has been approved for military use in China.
- LNP- encapsulated mRNA (Moderna/NIAID in the U.S.) based on RNA from the COVID-19 virus
The U.S. government’s ‘Operation Warp Speed’ programme is expected to name five or more vaccine projects, to receive billions of dollars in federal funding, even before there is proof that the vaccines work. This is aimed at fast tracking the whole process.
In India, two vaccines are in the works for phase I/II trials: Covaxin by Bharat Biotech and another by Ahmedabad-based Zydus Cadila. According to Zydus, the potential vaccine showed a "strong immune response" in animal studies, and the antibodies produced were able to completely neutralise the wild-type virus.
Differentmethods are being employed in making the vaccine for COVID-19. Considering that there have been no vaccines for other coronaviruses such as MERS or SARS, it is still largely an unknown field. Viruses morph and evolve, and hence coming up with a definitive vaccine is quite difficult.
One of the methods is based on our immune system producing antibodies that fight the virus. For this reaction to take place, scientists realised that they did not need to inject the entire pathogen — just the fragment that triggers this reaction. These are now used against hepatitis B and shingles. Scientists can add a gene from the virus they want to fight, thereby making a viral vector, which then stimulates the immune system to make antibodies. This is a method being employed with the ChAdOx1-S.
Some groups are injecting pure DNA and RNA, which then is read by the cell's protein-building factories, and they make a viral protein. The protein, in turn, comes out of the cell, where immune cells make an antibody to fight it. This is a method that Moderna in the U.S. has used.
PITFALLS OF ACCELERATED TRIALS
Writing in the journal Vaccines last month, vaccine developer Stanley A. Plotkin and Arthur L. Caplan, a bioethicist at NYU Langone Medical Center, proposed starting challenge trials for the COVID-19 vaccine, which involves infecting vaccinated volunteers with the coronavirus. The procedure might cut months or years off the vaccine research, but would put test subjects at risk.
There is also the risk that accelerated tests could lead to missing potential side-effects. A vaccine for dengue fever, and one for SARS that never reached the market, were abandoned after some respondents were found to be more susceptible to severe forms of the diseases, not less.
Vaccine making needs sophisticated equipment. Microsoft founder Bill Gates has warned of a critical shortage of a vital yet forgettable component: medical glass. Without enough supplies of the glass, there will be too few vials to transport the doses that will be needed by billions.
BIG PLAYER INDIA
The recent announcement by the Indian Council of Medical Research that a vaccine will be released by August 15 created a furore. On July 2, the council’s Director-General Balram Bhargava told 12 institutions to “fast-track all approvals”. While some said the date paints a slightly nationalist agenda to the pandemic, others objected to the fixing of a date for the vaccine, which until recently was simply in pre-clinical trials, when vaccines that had been under more advance phases had not yet announced an official date.
However, in an interview with Indian Express, Lokesh Sharma, a scientist with ICMR, said: “It is not to be interpreted as a deadline. This is our aim, which depends on the cooperation of institutes. If we are going to start work, we should do so with an aim, and it should be of success.”
Soumya Swaminathan, Chief Scientist with the WHO, has expressed doubts about the vaccine being available by August 15 in an interview with India Today. "Most vaccine development projects take years to complete. But since we are in the midst of a pandemic, we have shortened the timelines. A very optimistic estimate is that it will take about 12-18 months to develop a vaccine against Covid-19, from the time you start your vaccine development process."
The unlisted Indian vaccine maker Bharath Biotech’s Covaxin received regulatory approval to start human clinical trials for its experimental shot. It is lined up to be tested on over 1,100 people in two phases from July.
Serum Institute of India (SII) has already started production of the vaccine candidate developed at Oxford University, even though the drug has not been licensed yet. Adar Poonawalla, chief executive officer of SII, told the German TV channel Deutsche Welle (DW-TV) that “the decision [to start production of the vaccine] was made solely to have a head-start on manufacturing and to have enough doses available. The distribution of the doses will only commence once the trials are successful”.
There are high expectations on India as a number of Indian firms are already key players in the global vaccine industry. SII is the world’s largest vaccine producer. Hyderabad-based Bharat Biotech has so far commercialised 16 vaccines, including one against H1N1, and sells products in over 65 countries.
- During the MERS epidemic in the Middle East, though only 2,494 people were affected, the fatality rate was as high as 37% (one out of three people died). 8,000 people from 29 different countries and territories were infected, and at least 774 died worldwide, over a period of about 8 months. COVID-19 has been less fatal, killing less than two people out of every 100 affected, but it has been far more virulent and resilient. It is feared that it may remain active for a much longer time and ultimately infect a vast numbers. Therefore, a vaccine is a must but the approach to the virus has to be accordingly different.
- While the earlier coronaviruses have helped in kick-starting trials for COVID-19 vaccines, they have not made the task any easier. Vaccine production itself is a long process, and fast-tracking it brings in complications. For example, Moderna's first crack at a Zika vaccine did not create a great immune response, yet in its second attempt, it was at least 20 times more potent, according to an article in Nature. One thing is certain, India is going to play a pivotal role in both creating and mass-producing the vaccines as it has the capacity to do so.
Author: Synergia Foundation Research Team