On Thursday, 3 July, the Indian Council of Medical Research (ICMR) made a claim of aiming to launch India’s indigenous COVID-19 vaccine by 15 August. The nodal research body put out a press release on 4 July, standing by its target and saying that its vaccine process was ‘exactly in accordance with globally accepted norms to fast-track the vaccine development for diseases of pandemic potential wherein human and animal trials can continue in parallel’.
As the medical and scientific community remains sceptical of the timeline, ICMR maintained in the press release, "While issues raised in public domain from time-to-time from commentators are welcome, as they form an important part of feedback loop, the best of India's medical professionals and research scientists should not be second guessed for their professionalism or adherence to the highest scientific rigour".
The vaccine candidate, Covaxin, is developed in partnership with Bharat Biotech International Limited (BBIL).
Is it possible to have a vaccine out in the public by Independence Day?
FIT spoke to virologist Dr T Jacob John and Global Health, Bioethics and Health Policy Researcher, Dr Anant Bhan.
“It is a visionary and optimistic claim. The intentions of releasing a vaccine soon are good but it seems unrealistic that it will be ready in just 45 days. Phase 1 and 2 could be done in 45 days, but not Phase 3.”Dr T Jacob John, virologist and former professor at the Christian Medical College, Vellore.
Dr Bhan added that this seemed “highly unlikely, not just for Covaxin, but for all COVID vaccine candidates.”
Missing Details
One of the primary issues with the latest claim is that it has all happened very fast.
On Monday, 29 June, the Central Drugs Standard Control Organisation had given approval to Bharat Biotech to conduct clinical trials. And just 4 days later, on Friday, 3 July, the news is that a launch date for the final vaccine has been set.
Now as FIT explained earlier, vaccine production is a lengthy process purposely made so to ensure safety and efficacy.
Even with the fast-track approach to vaccine candidates in the pandemic, the big question remains: Is ICMR’s claim of a vaccine by 15 August scientifically possible?
Dr John tells me, “It’s best not to push science this rapidly.” He explains the various, important steps needed to make a vaccine. Dr Bhan also adds that “due process must be followed for a safe and effective vaccine.”
“When you are thinking of creating a vaccine, the simplest approach is to grow the virus and inactivate it. Hepatitis A, Influenza vaccine are all inactivated or killed vaccines. While the rest of the world is looking at other types of vaccines, Bharat Biotech decided to wisely go for whole-virus killed vaccines,” says Dr Jacob.
Pre-clinical studies, that is animal-testing, have been completed according to the statement by BBIL. But those pre-trial details have not been made public.
“I believe these preclinical results are safe and immunogenic - that means it induces antibodies in the animals. Bridging from animal studies to human studies normally will go through Phase 1, 2 and 3. If you plan well, you can combine Phase 1 and 2.”Dr T Jacob John, virologist and former professor at the Christian Medical College, Vellore.
He further explains, “Phase 1 is for safety, Phase 2 is for preliminary data on antibody production and Phase 3 is for protective efficacy or biological effectiveness in the field.”
So we need to go from Phase 1 to Phase 3. This happens when safety and immunogenic efficacy are documented and proven.
“Then, they have to go through a rapid Phase 3 trial to know if the vaccine offers protective efficacy. That cannot be done in 45 days.”Dr T. Jacob John, virologist and former professor at the Christian Medical College, Vellore.
Phase 3 needs to be done in fairly large populations in multiple locations where the epidemic is in the growth phase. “This is important as we can then calculate the risk of infection in the population and therefore also the protective efficacy due to vaccination,” says Dr Jacob. “This is then a sophisticated statistical epidemiological venture.”
Another issue that came up is the lack of clarity on why the centres mentioned in the ICMR letter were chosen to host the trials. Are the clinical trial sites ready?
“The Phases need 24 x 7 oversight, and they are usually done in tertiary centres with experience in conducting clinical trials. A lot of the sites mentioned in the letter are smaller centres, one would need to check if they have the required infrastructure and expertise,” says Dr Bhan.
He adds that there is a discrepancy in the dates of the enrolment in the trial, “ICMR says 7 July but the CTRI entry date is 13 July. Even if we assume this to be the second week of July, having a vaccine out by 15 August seems highly unlikely and improbable.”
Dr Jacob says that Phase 1 can also be done in just 20 people, and if found safe, can be expanded to 100 people. “We need to measure the antibody response through the Elisa technique of virus neutralising antibodies.”
Even Phase 1 and 2 to be done in 43 days now is cutting it fine, but “provided BBIL is willing to go through it in a rapid fashion and ICMR and NIV lend support, it can be done.”
As per their letter, ICMR has called this vaccine development “their topmost priority.”
Still, in 43 days, with Phase 2 done, it would still be a “vaccine candidate and not a vaccine,” says Dr Jacob.
New Vaccine for a New Virus
COVID-19 vaccine development is brand new territory both in terms of the virus and the vaccine.
“See COVID-19 is a peculiar virus, and some people over-respond to the infection.” Dr Jacob is talking about a cytokine storm when your immune system is in overdrive. “Will the inactivated virus be absolutely safe from those problems? We have burnt our fingers in the past with a killed virus vaccine. It's not always safe.”
“There needs to be even more attention to safety because this is a new vaccine for a new virus.”Dr Anant Bhan, Researcher, Global Health, Bioethics and Health Policy
“Of course, we are hoping an inactivated vaccine would be a safe and effective vaccine. But there is no proof of principle for the coronavirus,” says Dr Jacob.
“The coronavirus has a complicated virtual structure, therefore unwanted immunostimulation is a potentially possible response in humans. So if we go straight from animal studies to human studies it has to be carefully done.”
What About Safety?
One big question is why this is happening, and why these precise times are set, says Dr Bhan.
There is data and safety monitoring board - DSMB - which comprises independent experts who, as the name suggests, monitor participant safety in an ongoing clinical trial. They also ensure that the data is being collected properly.
“They have to certify that they are satisfied that this killed virus will not produce adverse reactions either directly with the vaccine or if somebody gets infected with live coronavirus,” says Dr Jacob.
There are two issues of safety: One is safety for the vaccine and one is the safety of the vaccinated person when they are exposed to coronavirus.
“An immunised person with live infections should not have a worse reaction than the disease itself. Dengue virus -Dengvaxia- vaccine had to be withdrawn because of that problem.”Dr T Jacob John, virologist and former professor at the Christian Medical College, Vellore.
So to test for safety one has to check three things says Dr Jacob.
Safe in general
Safe from unwanted immune responses
Safe when the person is infected with the virus
The push to produce results could be as COVID-19 continues to hold a grip over a nation, and we are still in one of the more strict lockdowns in the world. “We miscalculated how much it would harm us, and yes a vaccine would help us overcome this. It is a good intention but ultimately unrealistic,” says Dr Jacob.
What could be the ramifications of this fast-track approach? “It could raise concerns that we might miss out on due process, and that could lead to a potential safety and efficacy issue later on.” Would this be unsafe for the population that takes the vaccine? “We don’t know,” says Dr Bhan, “It could. Ensuring adequate processes will lessen the likelihood it could be.”
It comes down to this: Due processes exist for a reason and scientists should not be pushed beyond their boundaries to get fast results.
“As far as I am concerned, it needs to be tested throughly for safety and effectiveness before it is launched.”Dr T Jacob John, virologist and former professor at the Christian Medical College, Vellore.
(This story was first published on FIT. You can read the original article here.)
(At The Quint, we are answerable only to our audience. Play an active role in shaping our journalism by becoming a member. Because the truth is worth it.)