A battery of effective vaccines has been developed, thanks to an unprecedented year-long effort by vaccinologists worldwide. Currently, a major point of discussion is whether the start of vaccination is also the beginning of the end of the ongoing coronavirus pandemic.

As with most infections, on getting infected with SARS-CoV-2, the body triggers a specific immune response. Most easily detectable signatures for it are different antibodies circulating in blood generated by specific immune cells called B cells.

A large number of these antibodies are supposed to protect from propagation of the virus within the body, as they target viral components essential for infecting human cells, most critical of them being the spike protein of SARS-CoV-2.

Sero-surveys world-wide have reported variably stable antibody response in recovered patients, sustaining for almost six months. But circulating antibodies are not the sole ammunition for protecting against re-infections — T cells that specifically recognise viral components are also expanded in response to infection. Some T cells largely work by helping B cells produce antibodies and generate longer term memory (pools of rather quiescent B cells with ability to ramp up antibody production on repeated encounters with the virus).

In fact, it has been shown that conversion of SARS-CoV-2-specific B cells to the so-called ‘memory’ ones continue even at six months post-infection. Some other T cells work by directly killing cells in the body infected with virus, preventing spread within the body. T cells also generate memory pools which spring back to action on future encounters with the virus.

A recent study confirmed persistence of such T cells in circulation even eight months after infection. Keeping with these diverse arsenal of immune mechanisms, till date no considerable accounts of re-infection have surfaced anywhere in the world, until January this year. There might be at least two mutually non-exclusive reasons for this.

Sero-conversion

The population level of sero-conversion might have reduced transmissions and the immune protection induced by the initial infection might have worked well in the past year. But a disturbing piece of data has come from Brazil. In Manaus, the largest city in the state of Amazonas, almost 76 per cent of the population had antibodies against SARS-CoV-2 out of natural infection by October 2020.

The first peak of infections in Manaus was back in April 2020 and since June 2020, when estimated sero-prevalence was already more than 50 per cent, the hospitalisation rate due to Covid was stably low. But the city experienced a six-fold increase in hospitalised cases in January 2021 from December.

Manaus data has left scientists perplexed. There is possibility of wrongly estimated sero-prevalence data to start with. This might also have happened due to gradual waning of the antibody response by December, at close to seven months since the time infection rate remained stably low.

Viral variants

The third, more ominous, possibility is that recent infections are by viral variants which are not amenable to the protective antibodies induced by the original strain. Some of these newly emerged variants have accumulated variable number of mutations in the gene for the spike protein and thus may affect recognition by antibodies that were raised against unmutated spike.

The UK strain or B.1.1.7, the South African variant B.1.351 and the Brazilian variant P.1 have specific mutations which have ability to change the structure of the spike in a way that defy recognition by antibodies. Both B.1.1.7 and P.1 have been reported from Brazil in January. We are yet to get any dependable data on how these variants would respond to the T cell immunity generated against the original strain.

What do all these mean for the future of this pandemic? Can vaccines change the course of the pandemic? There are no easy answers to these questions. This is because there are a lot of unknowns about the vaccines, in terms of durability of immunity as well as their efficacy against variants.

What we know about the vaccines are that the ones already approved for emergency use are capable of generating immune response, in terms of both antibody generation and T cell immunity, quite similar to the natural infection. If the duration of protection with these vaccines is also like the natural infections then they will definitely influence the course of the pandemic greatly. It will be even better if they induce a formidable memory response among both B and T cells, data for which is still awaited.

We also do not know whether vaccinated individuals will stop the spread of the virus. Vaccine-induced halt in transmission requires a so-called sterilising immunity. But usual experience with viruses causing mucosal infections tells us that sterilising immunity is not something we would get in this case too. The immunity conferred by vaccines will perhaps prevent us from getting really bad disease and restrict most infections to being asymptomatic. But the infection will perhaps keep getting transmitted to un-vaccinated people and in the vulnerable may cause severe disease as well.

Vaccine efficacy

We need information on the vaccines’ efficacy against the viral variants. Some of them, like B.1.1.7, have been found to be equally affected by available vaccines made by Pfizer, Moderna as well as India’s Covaxin.

Pfizer’s vaccine has also found to be reasonably effective against the South African strain B.1.351, which is particularly notorious for its mutation profile. Covaxin, which is essentially inactivated whole SARS-CoV-2 virus injected along with adjuvants and targets viral proteins other than spike, should be more broad-spectrum in inducing immune response. Thus, theoretically speaking this one should also offer wider protection against variant strains. But, as with most others, the duration of such protection is not yet known for Covaxin too.

But keeping in mind the rather short duration of protective immunity even against the natural infection, as well as the expected timeline that can ensure considerable vaccination coverage worldwide, perhaps the virus is here to stay — even if not to pandemic proportions.

Rather, the virus’ staying around will perpetuate cycles of natural immune response, which will definitely get better with time. This is the case for most infections that we contract.

There will still perhaps be pockets of vulnerable populations that will contract infections that will lead to symptoms, but with time such symptomatic infections will also keep on getting milder. In fact, this is precisely what our experiences with other human coronaviruses have been.

Coronaviruses causing common cold in humans perhaps also had been a similar menace ages back, causing severe diseases in vulnerable sections of the population. But now the disease caused by them has become commonplace without much disruption in our daily life.

Thus, the pandemic is far from over and will perhaps take to a slow transition to endemic infections occurring in pockets and causing milder disease outcomes with time. We should take note of this very likely possibility and get used to the new normal social behaviour we have become so good at over the last year or so.

The writer is a physician scientist and immunologist in CSIR-Indian Institute of Chemical Biology, Kolkata.

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