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Will I Need A Fourth Dose Of COVID Vaccine? Perhaps Not, Suggests Trial


Dr. Katie Spalding

Katie has a PhD in maths, specializing in the intersection of dynamical systems and number theory.

Freelance Writer

COVID-19 vaccine

Three doses of an mRNA vaccine provides great protection, but a fourth dose may not be worth it for most, a recent trial suggests. Image: insta_photos/

About two in every three Americans is now fully vaccinated against COVID. More than two in every five of those Americans has had a booster shot. And as of last week, the US Food and Drug Administration (FDA) has confirmed that we may even see a fourth booster shot rollout this Fall. So you might be wondering: how long is this going to last? Is there some magic number of vaccine boosters that we need to beat the coronavirus, or are they just going to become a regular part of life?

One recent study may hold some clues. In Israel – one of a handful of countries where fourth booster shots have already been made available – some evidence has been found that a fourth shot may not provide that much extra protection after all.


“The third dose is really, really important … [but] people who are young and healthy and don’t have risk factors will probably not benefit much from a fourth dose,” explained Gili Regev-Yochay, a physician and infectious-diseases researcher at Sheba Medical Center in Ramat Gan, Israel, in an article for Nature. She’s lead author of the study, not yet peer-reviewed, which seems to suggest three shots of an mRNA vaccine provides an upper limit on immunity against COVID-19.

Nevertheless, she agreed with other researchers that for people in high-risk groups, a fourth shot would likely still be beneficial. While the extra dose may only replenish waning antibodies, epidemiologist Sara Tartof told NPR, “if you have an overall higher risk of hospitalization, this waning might cause a bigger impact than for somebody who has an overall very low risk of severe disease to begin with.”

Regev-Yochay and her colleagues recruited more than 1,000 healthcare workers for their trial, all of whom had received two doses and a booster shot of the Pfizer-BioNTech mRNA vaccine at least four months earlier. A fourth shot of either the Pfizer-BioNTech or Moderna vaccine was then given to 274 of the study participants, with the remaining volunteers acting as a control group.

But when they measured antibody levels in the participants’ blood before and after the fourth dose, they found something important. While the extra shot had increased these levels, the concentration of neutralizing antibodies did not surpass the levels seen after a third dose.


“I think what's happening is we're just reaching a threshold with this vaccine,” University of Chicago immunologist Jenna Guthmiller, who was not involved in the study, told NPR. She’s one of many researchers now convinced that the ever-evolving nature of COVID-19 might be limiting the effectiveness of vaccines now designed more than a year ago.

“Omicron, in my opinion, has changed everything,” Guthmiller said. “This virus is way more likely to cause an infection, and so what worked for previous variants, such as alpha and even delta, is perhaps not the same vaccine that's going to be necessary for omicron.”

The trial results bear that out: while participants who received a fourth dose did gain some extra protection against infection with the latest variant of concern, the increase was not particularly substantial. A four-dose course of Pfizer-BioNTech vaccine was 30 percent more protective than a three-dose course, the researchers found, and for Moderna, the increase was just 11 percent.

But while this may sound like bad news, University of New South Wales computational immunologist Miles Davenport sees it differently – the small increase in efficacy from a fourth dose of the vaccine is likely just because protection is “already quite high” after three doses, he told Nature.


“You can’t keep boosting antibody responses forever,” he said.


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