Using the same arm for multiple vaccine doses could provide faster protection during disease outbreaks, according to new research that reveals how vaccination site affects immune response development.
The study, published March 10 in The Journal of Immunology, found that mice receiving both doses of a COVID-19 vaccine in the same limb developed protective antibodies more quickly than those vaccinated in different limbs, though both approaches ultimately provided similar immunity levels.
For healthcare providers managing vaccination campaigns during pandemics, these findings suggest a simple but potentially significant optimization to current practices.
“Our findings suggest that during disease outbreaks when rapid immune protection is crucial, healthcare providers may want to consider administering multiple vaccine doses in the same arm,” said Dr. Jennifer Juno, co-lead author from The Peter Doherty Institute for Infection and Immunity at the University of Melbourne.
A Closer Look at the Immune Response
Most adult vaccinations are delivered into the muscle of the upper arm, and people typically choose their non-dominant arm for convenience. But little attention has been paid to whether receiving subsequent doses in the same or different arms affects how quickly protection develops.
When vaccines are administered, the immune response begins in lymph nodes closest to the injection site. These lymph nodes serve as training centers where specialized B cells learn to recognize the pathogen and produce protective antibodies.
Using a mouse model, researchers administered two doses of a COVID-19 vaccine fourteen days apart. One group received both doses in the same limb (called “ipsilateral” vaccination), while the other group received doses in different limbs (“contralateral” vaccination).
The team then measured antibody development at days 19 and 28 after the initial vaccination. Mice receiving both doses in the same limb showed faster antibody production immediately following the second dose. However, by day 28, both vaccination approaches resulted in similar overall immunity levels.
Potential Benefits During Outbreaks
These findings could have particular relevance during the early stages of disease outbreaks, when establishing immunity quickly across a population is critical.
“This knowledge could inform vaccination strategies not just for COVID-19, but for other vaccines that require multiple doses,” explained Dr. Hyon-Xhi Tan, co-lead author also from the Doherty Institute. “The findings provide valuable insights into how the immune system responds to vaccines in different locations, aiding in the development of more effective vaccination protocols.”
The researchers also explored whether vaccine location might influence immune response when targeting different variants of a pathogen. They found that mice vaccinated in the same limb with vaccines designed for different COVID-19 variants produced a greater breadth of initial antibodies.
“A greater breadth of initial antibodies was produced when vaccinated with SARS-CoV-2 variants in the same limb,” the researchers noted. “This indicates that an ipsilateral vaccination strategy could also be relevant in outbreak responses as viruses evolve or mutate.”
The Science Behind the Finding
What explains this faster antibody response? When vaccines are administered to the same site, the second dose activates immune cells already present in nearby lymph nodes from the first dose. This appears to create a more efficient immune response in the crucial early days after boosting.
The researchers observed that immune structures called germinal centers—specialized sites within lymph nodes where B cells mature—behave differently depending on vaccination location. In mice receiving both doses in the same limb, these centers remained active longer, potentially supporting faster antibody development.
Using advanced imaging techniques, the team tracked how immune cells in different lymph nodes responded to the vaccines. When both doses were given in the same location, they found evidence of sustained immune activity, while different-limb vaccination created separate, independent responses in different lymph nodes.
From Lab to Clinic
Though conducted in mice, these findings align with observations from human studies. A retrospective study of over 2.6 million COVID-19 vaccine recipients found increased protection against infection in the first month following vaccination in the same arm compared to alternating arms.
The research team is now investigating the biological mechanisms that drive this accelerated immune response. “We also want to determine if these findings extend to other vaccines, explore how the timing between doses affects location-based immune responses, and if other vaccine sites such as the lung impact this effect,” said Dr. Tan.
While both vaccination approaches resulted in robust long-term immunity, the researchers emphasize that the faster initial protection from same-arm vaccination could make a meaningful difference during active outbreaks.
For the average person heading in for their next multi-dose vaccine series, the message seems clear: consistency in arm choice might help your body build protection more quickly, though you’ll ultimately be well-protected either way.
The findings add to growing evidence that seemingly minor aspects of vaccine administration—like injection site—can meaningfully influence immune response development, offering potential ways to optimize vaccination campaigns during future disease outbreaks.
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