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 reduce protection from being infected with the omicron variant again for some people — and there’s a reason for that, new findings suggest.
In contrast, two vaccine doses, followed by an initial omicron infection, may protect more against a second omicron infection than an additional 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 in the immune system, researchers concluded.
Here’s what the findings mean.
“If you were infected with Omicron at any time, a third vaccine dose effectively doubles your dose risk of reinfection compared to just 2 doses,” Dr. Daniele Focosi, who specializes in hematology and works at Pisa University Hospital in Italy, wrote on Twitter in response to the findings. “Incredible Immune Defense at Work.”
The study points to immune imprinting as the reason why “three-dose vaccination was associated with reduced protection compared to two-dose vaccination.”
But what exactly is immunoprinting?
Fortune explains it as “a phenomenon in which an initial exposure to a virus — such as the original strain of COVID, by infection or vaccination — limits a person’s future immune response to 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 onset of the omicron wave from December 19 to September 15.
The study found that when looking at participants who had received three vaccine doses and had also previously been infected with an omicron subvariant, they experienced more reinfections than participants who had only received two doses.
“This finding suggests that the immune response to the primary omicron infection was compromised by differential immune imprinting in those who received a third booster dose, consistent with new laboratory science data,” the authors wrote.
Researchers note that none of the participants’ reinfections were severe, which “was not unexpected given the lower severity of omicron infections.”
A previous study examining immune imprinting and updating of covid-19 vaccines suggested that “repeatedly updating” the shots “may not be fully effective” because of the limitations that immunoimprinting can present. The work was published in November 2021 in the journal Trends in Immunology and appears in the National Library of Medicine online.
The national Qatar study emphasized that its findings “do not undermine” the benefits booster doses provide to the public, but researchers concluded that these benefits may be short-term.
“There is no doubt that the booster dose reduced the incidence of infection immediately after administration… Nevertheless, findings indicate that short-term effects of boosters may differ from their long-term effects,” the authors wrote.
The study acknowledges some limitations, including how they looked at recorded reinfections and how some infections could have occurred without being recorded.
The preprint study comes two months after the Food and Drug Administration approved new booster doses, called bivalent boosters, made by Pfizer and Moderna that target the omicron subvariants BA.4 and BA.5.
More about immunoprinting
In terms of immune imprinting, Medical News Today reports that “the ways our immune system 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 of these things push and pull your immune repertoire, your antibodies and things in different directions, and make you react differently to the next vaccine that comes along. […] So that is what is called immune imprinting, says Professor Danny Altmann of Imperial College London, who specializes in immunology, to the newspaper.
Because of this, the way one person may respond to an exposure to the virus can “vary significantly” compared to the next person, according to Medical News Today.
Fortune points to two recently published studies that cite “‘immune imprinting’ as a potential reason” why the new COVID-19 boosters targeting omicron may not be able 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 that “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 United States, about 7% of the total population, have received the latest bivalent COVID-19 booster dose, according to the Centers for Disease Control and Prevention. Meanwhile, nearly 227 million people have completed their primary series with either one or two doses.
The CDC advises everyone to stay current on their COVID-19 vaccines.
This story was originally published November 3, 2022 12:18 p.m.