A number of wealthy nations have decided to press ahead with plans to administer COVID-19 vaccine boosters in the coming months, to strengthen waning antibody responses in their most vulnerable groups. This week, the US Food and Drug Administration (FDA) approved giving boosters to people with compromised immune systems.

Many, including the World Health Organisation (WHO) have criticised the ethics of such booster campaigns when so many people around the world, especially in under-resourced countries, are yet to receive a first dose.

However, the vaccines are still providing high levels of protection, particularly against severe disease.

"I understand the concern of all governments to protect their people from the Delta variant. But we cannot accept countries that have already used most of the global supply of vaccines using even more of it," said WHO Director-General Dr Tedros Adhanom Ghebreyesus at a press briefing on 4 August.

As of May, high-income countries had administered around 50 doses for every 100 people, and that number has since doubled, Dr Tedros added. However, in low-income countries, a lack of supply has limited this to just 1.5 doses for every 100 people. Just 1.1 per cent of people in low-income countries have received their first jab, which is not even enough to cover healthcare workers, let alone other highly vulnerable populations.

WHO had previously criticised countries for vaccinating their adolescents when vulnerable elderly people in low-resource countries were still unvaccinated.

Those pursuing booster campaigns say they’re needed to shore up immunity against COVID-19 in people with weaker immune systems as winter approaches. Yet, hoarding vaccines for booster shots and leaving so many people around the world unvaccinated could undermine the very protection they’re seeking to reinforce.

Not only that, but most people being hospitalised or dying from COVID-19 are unvaccinated. Giving already-vaccinated people booster shots is unlikely to shift that pattern.

Waning antibodies

Certainly, there is some evidence that levels of neutralising antibodies begin to wane in the months after vaccination or infection, and these antibodies diminish faster in some individuals than others. Certain people, such as organ transplant recipients who must take immunosuppressive drugs, have a weaker response to vaccination in the first place.

According to new research published in the New England Journal of Medicine, delivering a third dose of mRNA vaccine to organ transplant recipients two months after their second dose resulted in substantially higher levels of antibodies, compared to those given a placebo.

Another recent study, which has not yet been peer reviewed, found that levels of neutralising antibodies had fallen substantially among adults aged over 60, six months after receiving two doses of Sinovac’s COVID-19 vaccine. However, delivering a third dose eight months after the second triggered a rapid increase in the levels of antibodies.

By blocking the coronavirus from entering our cells, such antibodies play a crucial role in preventing infection. However, they are not the only component of the immune system to be stimulated through vaccination, and it is still unclear whether this fall in neutralising antibodies correlates with a reduction in vaccine effectiveness – or how low levels of neutralising antibodies would need to fall for vaccine effectiveness to take a hit.

Also important are T cells – immune soldiers that recognise and destroy infected cells. Researchers have found evidence of robust T cell responses at least six months post-infection, and that even if people become re-infected with coronavirus, this T cell memory – which is also triggered by vaccines – could prevent many of them from becoming seriously ill. Memory B cells, capable of churning out fresh antibodies against SARS-CoV-2 if a person is re-infected, have also been detected 6 months after people have recovered from COVID-19, even when neutralising antibodies have significantly decreased.

Breakthrough infections

With a growing number of adults in wealthy countries fully vaccinated, it is increasingly clear that a minority can and do still catch COVID-19 – so-called breakthrough infections. And with the Delta variant increasingly making up a large proportion of infections in many countries, countries are concerned that existing doses won’t offer enough protection.

However, the vaccines are still providing high levels of protection, particularly against severe disease. If we knew the level of antibodies or T cells needed to prevent people from becoming seriously ill, public health authorities could consider administering booster shots if they saw evidence of protection dropping towards this level. These critical antibody and T cell levels required to confer protection are not yet known, so instead they must rely on observations of what proportion of infected, vaccinated people are admitted to hospital or sadly die from COVID-19. For now, at least, protection against severe disease appears to be holding up.

Variant factories

Worryingly, giving boosters could also prove short-sighted: the more people the virus infects, the more opportunity it has to develop mutations that could reduce the effectiveness of vaccines. This risk might be even greater if people with weakened immune systems are unprotected. Assuming they survive, they are more likely to experience prolonged infections, and during the course of their treatment, their viruses may evolve further mutations that help it to overcome some of our immune defences.

New variants can often spread faster and can sometimes be more deadly than previous versions of the virus. A number of case studies have now demonstrated the emergence of some of the same mutations found in the Beta and Gamma variants during the treatment of immunocompromised patients with persistent COVID-19 infections – such as the E484K mutation, which is believed to reduce the effectiveness of some vaccines.

"With the emergence of new variants, if we continue to leave the majority of the world unvaccinated, we will most definitely need adjusted vaccines in the future," as Dr Elin Hoffmann Dahl, infectious diseases medical adviser to Medecins Sans Frontieres' access campaign, told Reuters.

Of course, there is also a chance of this happening if immunocompromised individuals in wealthy countries are not offered booster doses. But it may be wise to delay the rollout of boosters to large numbers of relatively healthy older adults, until we have more data on whether they are even necessary. Roll them out too soon, and people might start getting boosters that have no real benefit.

There are still many unknowns. Booster shots may be necessary to increase and extend immunity, but they may not, or they may only be necessary for certain groups of individuals. There is, however, one certainty: Across the world, tens of thousands are still dying of COVID-19 every week, and there are many millions who need a first or second dose of vaccine immediately. They cannot afford to wait.

TOPICS: COVID-19

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