The first vaccine was administered to the right arm. Which arm will the second booster shot be administered in? The answer is the right arm. Research findings show that if the additional vaccine is administered to the same arm as the first vaccination, a quicker and stronger immune response occurs compared to when it is given to the other arm.
Researchers from the Garvan Institute of Medical Research in Sydney, Australia, and the Kirby Institute at the University of New South Wales (UNSW) said, "It has been confirmed in experiments on mice and clinical trials involving humans that administering the first and second vaccine shots in the same arm can induce a faster and more effective immune response," in the international journal Cell on the 29th.
Vaccines induce an immune response by injecting pathogens or their components, which have been rendered non-toxic or significantly reduced, to prepare antibodies accordingly. This is similar to conducting virtual battles to learn about the enemy's strength before an all-out war.
When a vaccine is administered, an immune response occurs in the lymph nodes near the injection site. This is the process where the "memory B cells" in the lymph nodes recognize the antigens. When actual pathogens invade, another immune cell, the macrophage, awakens the memory B cells to rapidly produce antibodies.
Sometimes, a single vaccine shot does not sufficiently induce an immune response. In that case, a booster shot is needed. This was also the case during the COVID-19 pandemic. The research team observed the immune response induced by the booster shot in real time using cutting-edge microscopy technology.
Dr. Rama Dhenni of the Garvan Institute of Medical Research noted, "We have newly confirmed that macrophages in the lymph nodes near the injection site play a central role in inducing an effective immune response from the booster shot."
Observations revealed that when vaccinated, memory B cells move to the outer layer of the lymph nodes and closely interact with macrophages present there. Administering an additional vaccine to the same site allowed the already alert macrophages to efficiently capture the antigens and immediately awaken the memory B cells to produce high-quality antibodies.
Additional experiments on humans yielded the same results. The Kirby Institute conducted clinical trials administering the COVID-19 messenger RNA vaccines from Pfizer-BioNTech to 30 participants. Among them, 20 received their first and second vaccinations in the same arm, while the remaining 10 were vaccinated in each arm.
Trial results indicated that the group vaccinated in the same arm produced neutralizing antibodies to deactivate the virus much faster within the first week after the second vaccination. The antibody effectiveness against the Delta and Omicron variant viruses was also significantly better.
Dr. Mee Ling Munier of the Kirby Institute said, "Four weeks after the second vaccination, the antibody levels in the two groups became similar, but during the pandemic, the rapid immune response in the initial weeks could make a critical difference for herd immunity." The research team added that when responding to rapidly mutating viruses, receiving a booster shot in the same arm could help a significant portion of the population achieve herd immunity faster.
These research results were previously reported in a study conducted in 2023. Researchers from Saarland University in Germany analyzed data from COVID-19 vaccine recipients and found that the group receiving additional vaccinations in the same arm showed a much higher detection rate of immune cells (killer T cells). Two weeks after the additional vaccination, the detection rate of killer T cells in the group vaccinated in the same arm reached 67%, while it was only 43% in the group vaccinated in the opposite arm.
References
Cell (2025), DOI: https://doi.org/10.1016/j.cell.2025.04.005
eBioMedicine (2023), DOI: https://doi.org/10.1016/j.ebiom.2023.104743