Same arm, faster shield: study shows vaccine location for immune response

Based on the use of multiple vaccine doses with the same arm during a disease outbreak, the study reveals how vaccination sites affect the development of the immune response.
The study, published March 10 in the Journal of Immunology, found that mice receiving two doses of 1,900 doses of vaccine in the same limb developed protective antibodies faster than mice vaccinated in different limbs, although both methods ultimately provided similar levels of immunity.
For healthcare providers who manage vaccination campaigns during the pandemic, these findings suggest simple but potentially important optimizations to current practices.
“Our findings suggest that healthcare providers may want to consider taking multiple vaccine doses in the same department when rapid immune protection is critical during a disease outbreak,” said Dr. Jennifer Juno, co-director of Peter Doherty’s Institute for Infection.
Observe the immune response carefully
Most adult vaccinations are delivered to the muscles of the upper arm, and for convenience people usually choose their non-dominant arms. However, few people pay attention to the speed at which subsequent doses are affected by the same or different weapons.
When the vaccine is administered, the immune response begins at the lymph node closest to the injection site. These lymph nodes act as training centers where specialized B cells learn to recognize pathogens and produce protective antibodies.
The researchers used a mouse model to perform two doses of the 14-day vaccine. One group received two doses in the same limb (called “ipsilateral” vaccination), while the other group received doses in the different limbs (“contralateral” vaccination).
The team then measured antibody development on days 19 and 28 after the initial vaccination. Mice receiving both doses in the same limb immediately after the second dose showed faster antibody production. However, by day 28, both vaccination methods resulted in similar overall immunity levels.
Potential Benefits During Outbreaks
These findings may have special significance in the early stages of disease outbreaks and are crucial when immunity is quickly established in the population.
“This knowledge can not only inform vaccination strategies for Covid-19, but also inform other vaccines that require multiple doses,” explains Dr. Hyon-Xhi Tan, co-leader of the Doherty Institute. “These findings help develop more effective vaccination protocols for how the immune system responds to vaccines in different locations.”
The researchers also explored whether vaccine locations may affect the immune response when targeting different variants of pathogens. They found that mice vaccinated in the same limb with vaccines designed for different Covid-19 variants produced larger initial antibodies.
“When vaccinated with the SARS-COV-2 variant in the same limb, larger initial antibodies are generated,” the researchers noted. “This suggests that ipsilateral vaccination strategies may also be associated with outbreak responses as the virus develops or changes.”
The science behind the discovery
What explains this faster antibody response? When the vaccine is administered to the same site, the second dose activates immune cells that are already present in nearby lymph nodes. This appears to produce a more effective immune response in the critical early stages after the elevation.
The researchers observed that the immune structures in the lymph nodes are called germinal centers (specific sites within the lymph nodes) different depending on where the vaccinated is located. In mice receiving two doses in the same limb, these centers remained longer active, possibly supporting faster antibody development.
Using advanced imaging techniques, the team tracked the responses of immune cells in different lymph nodes to the vaccine. When both doses were given at the same location, they found evidence of sustained immune activity, while different LIMB vaccinations produced independent independent responses in different lymph nodes.
From the laboratory to the clinic
Although performed in mice, these findings are consistent with observations from human studies. A retrospective study of more than 2.6 million Covid-19-19 vaccine recipients found that protection against infection increased in the first month after the same arm was vaccinated compared to alternating arms.
The team is now investigating the biological mechanisms that drive this accelerated immune response. “We also want to determine whether these findings extend to other vaccines, explore how timing between doses affects location-based immune responses, and whether other vaccine sites such as the lungs affect this effect,” Dr. Tan said.
Although both vaccination methods lead to strong long-term immunity, the researchers stress that initial protection of homosurgery vaccinations is faster during active outbreaks.
This information seems clear to the average person heading to the next multi-dose vaccine series: Even though you will be well protected in the end either way, consistency in ARM selection may establish protection faster.
These findings add to the growing evidence that vaccine administration (such as injection sites) appears to meaningfully influence the development of the immune response, thus providing potential ways to optimize vaccination campaigns during future disease outbreaks.
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