‘Best to roll out vaccine without antibody testing’
Some delayed effects could still be there, but we have to wait for those to surface—this is why post-marketing surveillance, or post-regulatory-approval monitoring, is important.
The Centre has unveiled a tentative Covid-19 vaccine roll-out strategy, against the backdrop of leading vaccine candidates reporting high efficacy numbers even as aspects of trial have been questioned by experts. In an interview with FE’s Ishaan Gera, Dr K Srinath Reddy—cardiologist & epidemiologist, and president of the Public Health Foundation of India—dwells on a broad swathe of questions on vaccine science and policy. Edited excerpts:
How important is it to keep monitoring a vaccine’s effects post clinical trials?
In the AstraZeneca vaccine trial, we have had some adverse effects reported during the trial itself; but for the Pfizer-BioNTech candidate, while there was no adverse effect reported by the trial, immediately after its roll-out in the UK at least two people developed anaphylactoid reactions that can be fairly severe—these were people suffering from allergic ailments, in fact, they carried adrenaline pens. A warning was immediately put out that people with allergic disorders shouldn’t use these vaccines. This emphasises the importance of post regulatory approval monitoring.
Most vaccine candidates have a 42-day/75-day/128-day end-point monitoring. Is this adequate?
All the participants enrolled should be evaluated for at least six weeks, preferably two months, because any adverse event that could occur should have occurred by then. Some delayed effects could still be there, but we have to wait for those to surface—this is why post-marketing surveillance, or post-regulatory-approval monitoring, is important.
Is it better to consider universal vaccination rather than a R0-based herd immunity threshold (HIT) when it comes to vaccine coverage?
One of the problems in terms of the R0 for this particular virus is that we are not sure how much it represents the reality. It may represent a trend, but not necessarily the reality of what the HIT actually might have to be. Many infected have been asymptomatic, that is what we are finding from the sero-surveillance studies. What you are getting from the RT-PCR tests/RAT is the so-called number of infected persons, the basis of your R0 number. That doesn’t tell you about the people who have been actually infected, but not reported by testing because they were either asymptomatic or pre-symptomatic or didn’t get tested because they had very mild symptoms. Having said that, R0 depends on whether people are using masks, practising distancing, avoiding super-spreader events, etc. This doesn’t mean the herd immunity threshold can be lowered. What happens when people stop observing these all these precautions? Therefore, you have to go for, if not the worst case scenario, for at least 60-70% coverage.
If the duration of the protection from a vaccine is shorter than the period it would take to cover a target of, say, 60-70% of the population…
That is why you are looking at different goals for the vaccine programme. Your primary objective is to keep the healthcare and other essential workforce healthy enough so that they can continue service, even if the duration of protection is six months. The second is protection of the vulnerable people—the aged, people who have co-morbidites. The vaccine will reduce the risk of severe disease or death on exposure, even if the immune response is not enough to stop the onset of Covid-19. If you are able to manage in terms of essentiality of the vaccine-recipient or her vulnerability, in six months’ time you might have been able to—because of public health measures—reduce the transmission of the virus.
Third is can you actually reduce the infection rates with the vaccine—there, we are entering uncertain territory. These are systemic vaccines, preventing the virus from triggering severe or moderate illness when the virus enters the body. If you look at the outcome measures of the vaccine trials, they don’t use the phrase ‘to prevent SARS CoV-2’ infection; they talk about preventing Covid-19, the clinical state.
So, with the vaccine, the body is capable of mounting an effective, and almost immediate, response to counter the virus and prevent it from really causing any tissue damage. In that process, it may prevent the virus from replicating in the body, too. But, if some of the virus is sticking to the nasal mucosa or the throat, the big question is can the vaccine recipient still transmit it. It is likely that you may be able to reduce the transmission because the vaccine has controlled the pathology—the recipient is not coughing or sneezing, or because the viral replication has been stopped and not enough viruses are there to be transmitted. So, the likelihood of transmissibility being impacted is there, but by how much, we don’t know.
There have many instances where some recovered cases lost antibodies against SARS CoV-2 faster than others. Can this happen with the vaccines as well?
In the case of vaccines, firstly, your ‘viral load’ proxy is very well-standardised through dosage studies; therefore, your antibodies are likely to last longer. But, the immune response is just about antibodies; T-cell immunity matters a lot, too. Now, in some of the studies or trials, you may not be studying the T-cell immunity, and may be doing it in subsets. But, there are indications that T-cell immunity could be triggered. So, even if the antibody decays, then you still may have immunity. The memory immune cells recognise the virus challenges and trigger off a strong immune response.
Can a person receive, say, one dose of AstraZeneca’s and then switch to Pfizer?
You have to go by the data that you have. There is no study to tell whether vaccines can be combined for a vaccine-recipient. Now, a study has been proposed for an AstraZeneca-Sputnik V combination. This is important, because, say, the immune response from one dose of a vaccine fights off the pathogen proxy in the second dose without the proxy having triggered antibody etc production. Any combination has to be approved on the basis of trials. Also, its safety has to be proved on the basis of trials.
Should the government do an antibody test before you are trying to inoculate the population?
The problem here is, firstly, there can be a few false-positive antibodies because of cross-reactivity with other coronaviruses. Even if they’re not large in number, we do not know what that false positivity rate is in our population. Second, we do not know how long the antibodies in those who are detected with these are going to last. Third, we do not know whether they have developed enough cellular immunity to last longer than the decay of the antibodies. So, it is best to go ahead with immunisation without testing for existence of antibodies—that’s the policy recommended by most public health agencies and the WHO as well.
Western countries are experiencing a second or third wave. We have not seen resurgence on a similar scale…
We do not know exactly what the experience in India is going to be over the next few months; we still have to wait and see, particularly for northern India. But, it is true that virtually all of South Asia has had relatively lighter blow from Covid-19 than Europe or North America. In South East Asia, though the cases are going up now, they are also triggered by super-spreader events mostly. For India, we will get better estimates once we do the antibody survey. Or, possibly for a variety of factors, the illness may not have been anything more than mild or even asymptomatic, either because of the younger age or because of earlier acquired cross-immunity from other infections/vaccination. There could be multiple reasons why it is happening. Is the virus getting reduced in its virulence and infectivity, or are we better adhering to masking, distancing, etc—there is no definite proof of either. This South Asian puzzle needs to be investigated further.