Here’s one weird trick for making the most out of your next two-dose vaccine: get a shot in both arms. A recent study found evidence that a two-arm approach can noticeably, if modestly, improve the body’s immune response to covid-19 compared to two shots in the same arm. More research will be needed to confirm whether this method should become widely recommended for future vaccines, however.

Several studies have looked at the question of whether arm choice can affect the immune response to multi-dose vaccines. But these studies have either involved small sample sizes or were observational in nature (a study that looks back in time, rather than proactively following people)—limitations that make it harder to establish a cause-and-effect link. The overall picture has been mixed as well, with some studies finding a positive or neutral effect from vaccinating both arms and others finding a negative effect. 

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The new study was led by researchers from Oregon Health & Science University. And they were able to look at data from a relatively large research project—a project where people were randomly assigned to receive the original covid-19 shots in one arm or both (the latter is also known as contralateral boosting). The data also allowed the team to track people’s immune responses over a 14-month period, as well as their response to the earliest versions of the coronavirus and to the initial Omicron variant. To this day, the circulating strains of SARS-CoV-2 still belong to the Omicron lineage.

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They tracked the immune responses of nearly 1,000 participants, all of whom were confirmed free of covid-19 antibodies before vaccination. Those who had the second shot in their other arm produced slightly more antibodies to the coronavirus, the study authors found. This amplified response was seen with both the spike protein (which allows the virus to invade our cells) and other parts of the virus. The difference between the two groups also grew larger over time, which may explain why other studies that only looked at people’s initial immune response may have failed to find a clear benefit for different-arm shots.

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The researchers also looked at 54 pairs of people matched in age and other characteristics, and found that while antibody levels were similar between the two groups at first, those who got a shot in both arms eventually produced greater amounts of binding and neutralizing antibodies (these antibodies play a pivotal role in containing or even preventing infection), including to the Omicron variant.

“In previously unexposed adults receiving an initial vaccine series with the [Pfizer/Biotech covid-19] vaccine, contralateral boosting substantially increases antibody magnitude and breadth at times beyond 3 weeks after vaccination,” the authors wrote in their paper, published last month in the Journal of Clinical Investigation.

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Other studies will have to validate the results seen here, and it’s possible that a dual-arm strategy might not be optimal for every disease. A 2022 study in mice found that a booster flu shot in the same arm was actually better for immunity, for instance. But assuming that this effect is real for at least some infections, the modest boost in immune response could be especially important for immunocompromised people. Given enough evidence, it might eventually prompt a sweeping change in how we vaccinate people in general.

“I’m not making recommendations at this point, because we need to understand this a lot better,” lead author Marcel E. Curlin, an infectious disease physician at Oregon Health & Science University, told the New York Times. “[But] all things being equal, we ought to consider switching up the arms.”

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