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Editor’s Note: This article has been updated to remove a paragraph linking to a separate study conducted by the authors of the Qatar study.
A COVID-19 booster, specifically a third vaccine dose, may lower protection against getting infected with the omicron variant again for some people — and there’s a reason why, new findings suggest.
In contrast, two vaccine doses, followed by an initial omicron infection, may protect more against a second omicron infection than an extra jab, according to a preprint study published Nov. 1 to medRxiv, a server run by Yale, BMJ and Cold Spring Harbor Laboratory. This is due to a specific reaction within the immune system, researchers concluded.
Here’s what the findings mean.
“If you got infected with Omicron at any time, a third vaccine dose actually doubles your risk of reinfection compared to 2 doses only,” Dr. Daniele Focosi, who specializes in hematology and works at Pisa University Hospital in Italy, wrote on Twitter in response to the findings. “Amazing immune imprinting at work.”
The study points to immune imprinting as the reason why “three-dose vaccination was associated with reduced protection compared to that of two-dose vaccination.”
But what exactly is immune imprinting?
Fortune explains it as “a phenomenon in which an initial exposure to a virus — say, the original strain of COVID, by infection or vaccination — limits a person’s future immune response against new variants.”
Authors of the Qatar study wrote how they sought to investigate the “phenomenon” by analyzing COVID-19 data recorded in the country’s national databases during the beginning of the omicron wave on Dec. 19 through Sept 15.
The study found that when looking at participants who had received three vaccine doses and had also been previously infected with an omicron subvariant, they experienced more reinfections than participants who had only gotten two doses.
“This finding suggests that the immune response against the primary omicron infection was compromised by differential immune imprinting in those who received a third booster dose, consistent with emerging laboratory science data,” authors wrote.
Researchers note that none of the participants’ reinfections were severe, which was “not unexpected given the lower severity of omicron infections.”
A prior study that examined immune imprinting and updating COVID-19 vaccines hypothesized “repeatedly updating” the shots “might not be fully effective” due to the limitations that immune imprinting can present. The work was published November 2021 in the journal Trends in Immunology and appears in the National Library of Medicine online.
The national Qatar study emphasized that their findings “do not undermine” the benefits booster doses provide to the public, but researchers concluded these benefits may be short-term.
“There is no question that the booster dose reduced infection incidence right after its administration…Nonetheless, findings indicate that short-term effects of boosters may differ from their long-term effects,” authors wrote.
The study acknowledges some limitations, including how they looked into recorded reinfections and how some infections could have occurred without being recorded.
The preprint study comes two months after the Food and Drug Administration authorized new booster doses, called bivalent boosters, made by Pfizer and Moderna that target omicron subvariants BA.4 and BA.5.
More on immune imprinting
In regards to immune imprinting, Medical News Today reports that “the ways in which our immune systems may have been exposed to SARS-CoV-2 markers are myriad,” noting how people have received different vaccine formulations and have been infected with different COVID-19 subvariants.
“All those things push and pull your immune repertoire, your antibodies and things in different directions, and make you respond differently to the next vaccine that comes along […] So that’s what’s called immune imprinting,” Imperial College London Professor Danny Altmann, who specializes in immunology, told the outlet.
Because of this, the way one person may respond to an exposure to the virus can “vary considerably” compared to the next person, according to Medical News Today.
Fortune points to two recently published studies citing “‘immune imprinting’ as a potential reason” for why the new COVID-19 boosters targeting omicron may be unable to “outperform the original vaccine.” One involved Columbia University and the University of Michigan, and another involved Harvard University.
The Harvard affiliated preprint study published Oct. 25 on bioRxiv concluded “immune imprinting…may pose a greater challenge than currently appreciated for inducing robust immunity to SARS-CoV-2 variants.”
As of Nov. 3, more than 22 million people in the U.S., about 7% of the total population, have received the newest bivalent COVID-19 booster dose, according to the Centers for Disease Control and Prevention. Meanwhile, nearly 227 million people have completed their primary series of either one or two doses.
The CDC recommends everyone stay up to date on their COVID-19 vaccines.