Scientists debate fourth Covid vaccine dose as Omicron cases rise

A fourth Covid-19 vaccine dose offers protection for elderly people and those with health problems, a growing body of research suggests, but experts have found a lack of evidence to support rolling out a fresh round of jabs more broadly.

The UK, Germany, France and Sweden are among countries offering fourth doses to the elderly and vulnerable. In the US, Pfizer last week asked regulators to authorize a fourth dose for people over 65 while Moderna wants its jab to be available to all adults.

But the EU drug regulator has expressed doubts about the need for a fourth jab, requesting additional data and citing hypothetical concerns that repeated boosters could overload people’s immune systems.

Some experts warn that waning immunity from boosters and previous infections, along with a lack of restrictions, mean health services could be overwhelmed if a highly pathogenic variant emerges.

The debate over a fourth dose coincides with a surge in Covid cases in Europe linked to the spread of the highly transmissible Omicron BA.2 sub-variant.

Eric Topol, director of the Scripps Research Translational Institute, said data from Israel – which became the first country to give third and fourth doses – show that efficacy wanes after about four months.

“It’s exactly what we saw with the first shot,” he said, adding that it had been hoped a third dose might boost the immune system’s memory enough to provide long-lasting protection.

Israeli data on the efficacy of fourth doses differ depending on the age of the recipient. When Pfizer made its application to the US regulator, it said evidence from Israel showed that an additional booster dose increased immune responses while lowering infection rates and incidences of severe illness.

However, when Israel’s Sheba Medical Center gave its healthcare workers a fourth shot, it found it boosted antibodies but did not prevent infection with Omicron.

In interim findings published in the New England Journal of Medicine last week, the authors said that for young and healthy people, a fourth vaccine provided “little protection” above just having three doses.

This is why many countries are prioritizing older groups where they can get the most “bang for their buck”, Topol said.

The UK this week started administering fourth doses to the over-75s and those at highest risk. Professor Adam Finn, a member of the UK government’s Joint Committee on Vaccination and Immunization, said Omicron has created a “moving situation”. He is closely watching data to understand who is being hospitalized.

“If we go on having a lot of viral circulation, which is unhappily going back up again, we’re going to have a bigger problem,” he said.

Finn believes a wider booster rollout in the UK in the autumn is likely, ahead of a possible winter wave. “The present fourth dose booster is seen as a way of bridging between now and then, [for] the people who cannot make it safely to the autumn program, ”he said.

As some governments move to a posture of living with Covid, they may be satisfied with only revaccinating those most likely to experience severe disease.

However, some experts believe governments need to give out boosters to help health systems catch up on treating other conditions.

Penny Ward, visiting professor in pharmaceutical medicine at King’s College London, said even patients admitted with – but not because of – Covid require extra resources. Vaccines, antivirals and long-acting antibody treatment can all help alleviate this pressure.

“Allowing the situation to continue where the health service is completely overwhelmed with disease, now we have the tools to prevent it, is irrational,” she said.

But some scientists have expressed concerns that too many boosters could lead to “immune exhaustion” – a phenomenon in which repeated exposure to a pathogen over time diminishes the ability of immune cells to respond effectively.

“This hasn’t been demonstrated yet for Covid-19 but it’s something to study,” said Amesh Adalja, senior scholar at the Johns Hopkins Center for Health Security.

Health authorities that opt ​​to roll out boosters must decide whether to use the original vaccines or versions of the shots tailored to the Omicron variant that emerged in November.

“Continuing to boost with the same formulation of the vaccine may blunt the ability of the immune system to respond to new variants,” said Adalja.

In the coming weeks, vaccine makers BioNTech and Pfizer and Moderna are expected to publish the late-stage trial results of their Omicron-targeted shots. The data will show how effective the vaccines are against the variant.

But scientific advisers will have to weigh whether to switch to the tweaked jabs based on information that no one has: whether the next variant evolves from Omicron or a previous strain.

Theodora Hatziioannou, a virologist at Rockefeller University, said a paper she co-authored, which is yet to be peer-reviewed, shows that an Omicron infection boosted the antibodies of those who had two doses of the vaccine, but did not boost them for those who had had three doses.

She believes this may provide a clue about the added benefit of an Omicron-tailored shot. “If they have already had three doses, I don’t believe it is justified. If they have only had two doses then the updated vaccine is the best choice, ”she said.

Even if governments decide fourth doses are needed, it may be a struggle to convince people to be vaccinated again. Only about half of Americans who had two shots returned for their third. A survey of US adults who had received at least one Covid vaccination found that almost half would either “definitely not” get a booster or only do so if they were required to.

Ezekiel Emanuel, vice-provost of global initiatives at the University of Pennsylvania, said public health experts must consider what the public will tolerate. “The idea that every six months people are going to get a booster. . . that just is not going to happen. ”

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