Scientists debate fourth dose of Covid vaccine as Omicron cases rise
A fourth dose of Covid-19 vaccine offers protection for the elderly and people with health conditions, a growing body of research suggests, but experts have found a lack of evidence to support the rollout of a new round of vaccines wider.
The UK, Germany, France and Sweden are among the countries offering fourth doses to the elderly and vulnerable. In the United States, Pfizer asked regulators last week to allow a fourth dose for people over 65, while Moderna wants its jab available to all adults.
But Europe’s medicines regulator has expressed doubts about the need for a fourth hit, asking for further data and citing hypothetical concerns that repeated boosters could overload people’s immune systems.
Some experts warn that waning immunity from recalls and previous infections, along with a lack of restrictions, means health services could be overwhelmed if a highly pathogenic variant emerges.
The debate over a fourth dose coincides with an upsurge in Covid cases in Europe linked to the spread of the highly transmissible subvariant of Omicron BA.2.
Eric Topol, director of the Scripps Research Translational Institute, said data from Israel – which became the first country to administer the third and fourth doses – shows that effectiveness declines after about four months.
“That’s exactly what we saw with the first vaccine,” he said, adding that it had been hoped that a third dose might boost immune system memory enough to provide long-lasting protection.
Israeli data on the effectiveness of fourth doses differ depending on the age of the recipient. When Pfizer filed its application with the US regulator, it said evidence from Israel showed an additional booster dose increased immune responses while reducing infection rates and the incidence of serious illness.
However, when Israel’s Sheba Medical Center gave its healthcare workers a fourth injection, it found that it increased antibodies but did not prevent Omicron infection.
In tentative findings published in the New England Journal of Medicine last week, the authors said that for young, healthy people, a fourth vaccine offered “little protection” beyond just three doses.
That’s why many countries are prioritizing older age groups where they can get the most “bang for their buck”, Topol said.
The UK this week began giving fourth doses to over-75s and those most at risk. Professor Adam Finn, a member of the UK Government’s Joint Committee on Vaccination and Immunization, said Omicron had created a “shifting situation”. He closely monitors the data to understand who is hospitalized.
“If we continue to have a lot of viral traffic, which unfortunately is going up, we’re going to have a bigger problem,” he said.
Finn thinks a wider UK booster rollout in the fall is likely, ahead of a possible winter surge. “The current fourth dose reminder is seen as a way to bridge the gap between now and then, [for] people who cannot safely make it to the fall program,” he said.
While some governments adopt a posture of life with Covid, they may be content to re-vaccinate only those most likely to suffer from serious illness.
However, some experts say governments need to distribute reminders to help health systems catch up on treating other conditions.
Penny Ward, visiting professor of pharmaceutical medicine at King’s College London, said even patients admitted with – but not because of – Covid need extra resources. Vaccines, antivirals and long-acting antibody treatments can all help ease this pressure.
“Letting the situation continue where health services are completely overwhelmed with disease, when we now have the tools to prevent it, is irrational,” she said.
But some scientists have expressed concern that too many boosters could lead to “immune exhaustion” – a phenomenon in which repeated exposure to a pathogen over time decreases the ability of immune cells to respond effectively.
“It hasn’t been demonstrated for Covid-19 yet but it’s something to study,” said Amesh Adalja, principal investigator at the Johns Hopkins Center for Health Security.
Health authorities choosing to deploy boosters must decide whether to use the original vaccines or versions of the shots tailored to the Omicron variant that appeared in November.
“Continuing stimulation with the same vaccine formulation can dull the immune system’s ability to respond to new variants,” Adalja said.
In the coming weeks, vaccine makers BioNTech, Pfizer and Moderna are expected to release results from late-stage trials of their targeted Omicron vaccines. The data will show the effectiveness of vaccines against the variant.
But scientific advisers will have to weigh whether to switch to modified bites based on information 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 has yet to be peer-reviewed, shows that an Omicron infection boosted antibodies in those who received two doses of the vaccine, but did not stimulate them for those who had had three doses.
She thinks this may provide a clue to the added benefit of an Omicron bespoke shot. “If they’ve had three doses already, I don’t think it’s justified. If they’ve only had two doses, the updated vaccine is the best choice,” she said.
Even if governments decide a fourth dose is needed, it can be difficult to convince people to get vaccinated again. Only about half of Americans who had two shots returned for their third. A survey of American adults who had received at least one Covid vaccine found nearly half would ‘definitely not’ receive a booster or would only do so if they had to.
Ezekiel Emanuel, vice provost for global initiatives at the University of Pennsylvania, said public health experts need to consider what the public will tolerate. “The idea that every six months people are going to get a reminder . . . that’s just not going to happen,” he said.