Why Booster Shots Should Be in the Same Arm

By Wayne Persky

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A recently-published study led by the Garvan Institute of Medical Research and the Kirby Institute at the University of New South Wales in Sydney, Australia has revealed that the site of vaccine administration — specifically, which arm receives the shot, can significantly influence how quickly and effectively the immune system responds to a booster dose. The study was published in Cell on April 28, 2025, and it offers key insights that may shape future vaccine administration strategies (Dhenni, et al., 2025).1

The researchers discovered that administering a booster vaccine in the same arm as the initial dose leads to a faster and more robust immune response. This occurs because memory B cells (the immune cells responsible for producing antibodies) tend to remain in the lymph node closest to the original injection site. These cells are “primed” by local macrophages (a type of immune cell that captures antigens and alerts other immune cells), to create a small, localized environment ready to mount a rapid and robust antibody response when the same site is used for a booster injection.

Using advanced intravital imaging in mice (a technique that allows scientists to visualize and study biological processes at a cellular level within living organisms), the researchers found that these primed macrophages efficiently captured vaccine antigens and reactivated memory B cells, to significantly enhance the immune response. This biological advantage was then confirmed in human trials.​

Their test trial involved patients receiving Covid 19 booster vaccines.

In a clinical study involving 30 participants receiving the Pfizer-BioNTech COVID-19 mRNA vaccine, researchers compared immune responses between those who received both doses in the same arm versus different arms. Within one week of the second dose, those in the “same-arm” group produced faster and more potent neutralizing antibodies, especially against variants such as Delta and Omicron.​

While both groups had similar antibody levels by four weeks, the early immunity observed in the same-arm group could offer critical protection during the most vulnerable window of infection during a pandemic, or other rapidly-spreading virus risk. This insight is particularly important for controlling outbreaks of fast-mutating viruses, where early herd immunity can reduce transmission rates.

So the take home message is:

If you’re getting a vaccine booster, choosing the same arm as your first dose could give your immune system a head start. While long-term protection will level out regardless of the injection site, those initial weeks of stronger immunity could make a significant difference, both for individuals and the “herd effect” that's so important for public health outc

Reference

1. Dhenni, R., Hoppé, A. C., Reynaldi, A., Kyaw, W., Handoko, N. T., Grootveld, A. K., . . . Phan, T. G. (2025). Macrophages direct location-dependent recall of B cell memory to vaccination. Cell, Retrieved from https://www.cell.com/cell/fulltext/S0092-8674(25)00407-6