The science behind Covid-19 vaccine boosters: Do we really need an extra shot?

It was only earlier this year that “Have you been vaccinated?” became the standard greeting in many countries. Now, that is set to be taken over by: “Have you got your booster shot?”

Some countries, including Singapore, Israel, Germany and France, have started administering an additional dose of a Covid-19 vaccine to the elderly and the immunocompromised, as studies show waning immunity against the coronavirus over time after the initial shots.

The move has sparked debate over whether the boosters are truly necessary, and if doing so is ethical and equitable.

The discussion took a new turn this week as fresh data backed up earlier findings – yet to be peer-reviewed – that the efficacy of both Pfizer’s and Moderna’s vaccines declines in a matter of months, and that one more dose of the Pfizer shot can reduce the rates of infections by 11 times and severe illness by 20 times in the elderly.

There are many arguments both for and against boosters, but what concerns policymakers and health professionals first and foremost is whether the science shows that they are a necessity.

In considering this, we examine three key issues: Are immunity levels indeed dropping? Will extra shots really help and are they safe? What are the broader implications of giving another shot to those already vaccinated?

Immunity: Antibody levels and real-world data

Scientists typically look at antibody levels as a proxy for how well vaccines work. Early studies have shown that the levels of antibodies generated by the Covid-19 vaccines fall over time. But that is perfectly normal.

“There isn’t a vaccine where you don’t see a drop over time in antibody titres,” Professor Rafi Ahmed told scientific journal Nature, referring to the unit of measurement for antibodies.

“There is always a drop,” said the immunologist and director of the Emory Vaccine Centre in the United States.

It is not so much about the quantity of these antibodies, but their quality – whether they are effectively protecting the body from being ravaged by the invading virus. But how to measure this with certainty is less clear, scientists say.

“If you had high levels of antibodies to every pathogen that you come across, your blood would be sludge,” said Dr Jane O’Halloran, an assistant professor of medicine at the Washington University School of Medicine in St Louis. “Sometimes, the easy bit to measure is not the thing that gives us the best window into what’s going on in the body.”

With the science still murky on whether antibody levels are directly proportional to protection against infection and disease severity, experts have turned to examining real-world data.

A new study released by Moderna this week showed higher rates of infection among US volunteers vaccinated with its shots about 13 months ago compared with those vaccinated some eight months ago.

The vaccine maker also reported a trend towards a lower rate of severe cases among the more recently vaccinated, but said the finding was not statistically significant.

Recent studies in Israel, too, have shown that individuals vaccinated with Pfizer shots earlier in the country’s immunisation programme were significantly more likely to catch Covid-19 and even suffer severe illness from the virus as the months passed.

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Some experts point to other factors at play, such as the arrival of the more transmissible Delta variant and the fact that many of those earlier-vaccinated individuals were either healthcare workers who tended to be more exposed to the virus or immunocompromised people.

But others also note that Israel’s severe case count, which had shot up after the Delta strain arrived, has stabilised weeks after the roll-out of booster shots began in mid-August. New weekly hospitalisations have now dipped to around 1,200 from a peak of more than 1,400 in late August.

Risks: Side effects and immune exhaustion

There is little argument that booster shots elicit stronger immune responses. But with the initial doses already keeping most people out of hospitals, the benefits of getting one more jab may be only marginal for a large majority of individuals.

In Israel, nearly six in 10 of hospitalised Covid-19 patients had been fully vaccinated, reports showed last month. This is in part due to the country’s high vaccination rate, at 62 per cent of its whole population. But the data also revealed that almost 90 per cent of those hospitalised were older than 60 and had chronic illnesses.

Experts note that some immunocompromised individuals are simply unable to produce satisfactorily high levels of antibodies even after full vaccination. Even with a third dose, their antibody levels – while improved – tend to remain below those seen in other vaccinated groups, according to a study involving organ transplant patients on immunosuppressive drugs that was published last month in the New England Journal of Medicine.

These findings may make the scientific case for offering extra shots to the elderly and those with comorbidity, no matter how marginal the protection is. However, the jury is still out on whether healthy adults should get them too.

Trials so far suggest that the side effects of an additional jab will not be too different, Emory Vaccine Centre’s Prof Ahmed said. For most people, the side effects were mild, but a small proportion suffered more serious issues, such as blood clots and heart inflammation.

Each additional shot also brings with it the risk of immune exhaustion, meaning that the immune system learns to tolerate the virus rather than recognising it as a threat and working to destroy it.

“There’s obviously some risk in continuously trying to ramp up an immune response,” Dr Marion Pepper, an immunologist and associate professor at the University of Washington, told The New York Times. “If we get into this cycle of boosting every six months, it’s possible that this could work against us.”

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Broader implications

Essentially, in deciding whether or not to offer booster shots, policymakers have to keep in mind their end goal: Is it to prevent severe illness and deaths, to lower transmissions, or to stop infections altogether?

All three would be ideal, but which is the most critical?

The vaccines never promised to eradicate infections – the vaccinated can still get Covid-19 – so stopping them altogether would be a pipe dream in modern-day society with its porous borders and geographically mobile people.

There is some hope for lowering transmissions, though, as research so far has shown that those vaccinated may be less likely to get infected, and if they do catch the virus, they may produce lower viral loads and hence be less infectious to others.

If booster shots, in mounting a stronger immune response, can help further lower the chances – however marginal – of a fully vaccinated person getting infected or becoming more infectious, then that could also better protect members of the public, especially those who for medical reasons cannot get vaccinated.

“(A booster) will ultimately prevent others from going to the hospital, and it ultimately will benefit the way the country is going,” said Professor Michel Nussenzweig, an immunologist and senior physician at The Rockefeller University in the US.

Advisers to the US Food and Drug Administration have recommended Pfizer boosters for people aged at least 65 and those at high risk of severe illness, though they rejected granting broader approval, citing a lack of evidence in the US context.

If stronger data emerges or if the pandemic worsens, everyone may eventually require boosters. But until then, it appears to be good for some but not necessarily for others.

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Critics of booster roll-outs see countries offering extra doses at the expense of millions of others around the world who remain in dire lack of any doses at all as selfish and unfair. After all, no one can possibly need a third dose more than someone who needs his first.

But if we consider solely the science of the matter, it is little wonder that policymakers are leaning towards offering booster shots to some.

As Dr Dvir Aran, an assistant professor of biomedical data sciences at the Technion-Israel Institute for Technology, put it: “The risk is low, the advantage is high.”

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