In a study published in reputed medical journal the BMJ earlier this week, researchers from the Johns Hopkins Bloomberg School of Public Health noted that a quarter of the world’s population would be unlikely to have access to Covid-19 vaccines until 2022.
The global multilateral effort, COVAX, is meant to counter a situation exactly like this one, with the promise to provide fair and equitable access to vaccines. But the sequence in which vaccine manufacturers will fill orders is unclear. Will bilateral purchase obligations take precedence over multinational organisations?
Scroll.in spoke to K Srinath Reddy, president of the Public Health Foundation of India on how soon India could have access to vaccines and the potential challenges we face.
Three vaccine candidates have applied for EUA, emergency use authorisation, in India:
- The Oxford-Astrazeneca vaccine being manufactured here by the Serum Institute of India.
- Pfizer-BioNTech’s mRNA vaccine
- The indigenously developed Covaxin by Hyderabad’s Bharat Biotech.
It is reported that Indian regulators will wait for the assessment of the Oxford vaccine by the UK regulator before making its own. This vaccine, in all likelihood, will be the one available for phase 1 of vaccination in India. It is unclear though as to how many doses will be available.
Pfizer-BioNTech has asked for some more time to make a presentation before the committee. This vaccine is not seen as ideal for Indian conditions given the -70 degree storage and transport requirements
Bharat Biotech has only just begun phase 3 trials.
In this context, can we estimate a timeline within which the proposed 60%-70% of Indians could be vaccinated? Do you anticipate India may not have access to enough doses of whichever approved vaccines for a sustained, continuous vaccination effort?
Leaving aside the mRNA vaccines which are unsuitable for our nationwide cold chain dependent distribution, the earliest vaccine that may become available for us is the Oxford-AstraZeneca adenovirus vector vaccine that is being produced by the Serum Institute of India. That is subject to regulatory approval in the UK and India.
Once the health and other essential workers are covered, the vulnerable sections defined by age and disease will be covered. By the time this phase is ending, the Russian vaccine and Bharat Biotech vaccine may enter the supply chain, if cleared by the regulator. Other vaccines may follow in the second half of 2021.
The proportion of the population to be immunised and the speed of that effort need to be constantly reviewed based on the state of the epidemic and supply chain capacity. With proper planning and a good opening, I do not foresee a middle order collapse in cricketing terms.
According to Adar Poonawalla, chief executive of Serum Institute, by March or April 2021, the vaccine they are manufacturing (Oxford-AstraZeneca) will be available for private purchase. Will the government need to sign off on this? Given that supply will initially be limited, is it prudent for the available vaccine doses to be accessed by those that can afford it, as opposed to a thought out, reasonable priority based access?
I am not aware of the conditions under which an internationally developed vaccine was permitted for manufacture in India. Whatever has been agreed to as the commitment to Indian supply must be distributed in accordance to the public health guided priorities set by the government and not be distorted by private purchaser power of open market sale.
The curtailed time frame of the clinical trails and emergency approvals is unprecedented. Two questions that conventional phase 3 trials lasting years would have answered are:
- The duration of immunity or how long the vaccine will protect the vaccinated? (This concern is particularly being raised because of the odd cases of Covid reinfection that have been reported and the documented decline in antibodies within weeks of being naturally infected.)
- Delayed allergic/adverse reactions to the vaccine.
It is true that long-term adverse effects and duration of immunity conferred by the vaccine are not possible in short-duration trials. However, given the worldwide death toll and the disruption caused by the virus to economic and social life, an effective vaccine was sought with urgency. The cumulative data from phases 1, 2, 3 of the clinical trials give a reasonable assurance of safety.
The vaccines which are administered by the intramuscular route are not sterilising mucosal vaccines and provide protection against symptomatic disease and not against infection per se. The primary outcome measure in these trials is ‘symptomatic Covid-19’. Evidence of short-lived ‘infection‘ (without ‘disease’) may still be observed in some persons who are vaccinated.
It is argued that even if the antibodies decline after natural infection or vaccination, there may be longer lasting cellular immunity conferred by T lymphocytes. Memory T cells and B cells, which store the image of the viral antigen from the initial encounter, may lie latent but can get activated by the next encounter.
Bharat Biotech has applied for restricted emergency use. Phase 3 trials for this vaccine have only just begun. How does one weigh the risk vs benefit simply on the basis of phase 2 data. Is it ethical to grant approval – it has not happened yet – on the basis of the limited phases 1, 2 data.
Phase 3 data must be reviewed by the regulator before granting any authorisation for use outside of the trial population.
Should the government make the minutes of the meeting of the National Expert Group on Vaccine Administration public, in the interest of transparency and building the confidence of the people in whichever vaccine is granted approval?
Vaccine approvals are granted by the Drug Controller General of India. The National Expert Group on Vaccine Administration defines the priorities and pathways for vaccine administration in the population. The DCGI may reveal the rationale for the approval, once given. Ideally, wider scientific examination of the trial data should be ensured. That will inspire public confidence in any approved vaccine.
How do you view Haryana minister Anil Vij, a volunteer in the Bharat biotech trial, claiming that he knew that he received the vaccine? In a double blinded trial, how is it possible for the volunteer to know whether he got the vaccine or the placebo? The minister subsequently tested positive for Covid. Don’t episodes like these create doubts and fan vaccine hesitancy?
The minister may have recognised the active vaccine from the side effects he experienced. He had received only the first dose when he was diagnosed. He would not have yet acquired adequate immunity from that single dose. Such episodes must be clearly explained in the media and not left to speculation.
Apart from the challenges in securing enough vaccines, one anticipates a severe shortage of vaccinators. Unlike the polio oral drops, the vaccine will be an intramuscular jab. How are we or how should we be preparing to meet the shortfall of trained vaccinators?
This is certainly going to be a challenge. Apart from doctors and nurses who are already authorised to inject, medical and nursing students can be trained and deployed. If there is a shortage still, I would suggest that even the students qualifying in the National Entrance Examination Test for MBBS admission may be trained and pressed into service before commencing studies. That will give them both technical and soft skills of engaging with the community. Others, such as science graduates, too can be trained as vaccinators.
Astrazeneca is set to start clinical trials to test a combination of its vaccine and the Russian Sputnik V to determine if there is increased efficacy. Can you explain this?
Both of these vaccines are dependent on a harmless adenovirus virus acting as the carrier for transporting the gene related to the Spike protein of the SARS CoV-2 virus into the human cells. The Spike protein, made by the human cells thereafter, elicits the immunological reaction that confers acquired immunity to the virus which causes Covid-19. Since two doses of a vaccine are required to develop a good immune response, there is some concern whether the adenovirus carrier delivered in the first dose can evoke an immune response against itself. If that happens, the second dose may become ineffective because the body reacts against the carrier virus and does not permit it to deliver the Spike protein code.
The solution to such a problem may lie in using two different adenovirus carriers for the two doses of the vaccine. The Oxford Astra-Zenica vaccine uses a Chimpanzee adenovirus, while the Russian vaccine uses human adenovirus strains which are different. So, it has been proposed that the first and second doses could use two separate vaccines with different adenovirus carriers. In cricketing terms, the ball remains the same but there are different bowlers at the two ends.