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A new study suggests that receiving multiple doses of a vaccine in the same limb may lead to a faster antibody response, potentially enhancing immunity in critical situations such as disease outbreaks or pandemics.

The research, published in The Journal of Immunology, revealed that mice given both doses of the COVID-19 vaccine in the same limb (ipsilateral administration) exhibited a quicker initial antibody response compared to those that received the vaccine in different limbs (contralateral administration). Over time, however, both methods resulted in similar levels of immunity.

Dr. Jennifer Juno, co-lead author from The Peter Doherty Institute for Infection and Immunity at the University of Melbourne, emphasized the practical implications of these findings. “Our study suggests that during outbreaks, when rapid immune protection is essential, healthcare providers might consider administering multiple vaccine doses in the same arm to enhance early antibody development. This strategy could be particularly beneficial in pandemic situations where swift immune responses are crucial.”

Dr. Hyon-Xhi Tan, also a co-lead author from the same institute, added that the research offers valuable insights beyond COVID-19 vaccination. “These findings may inform broader vaccination strategies, as they highlight the impact of immune response dynamics based on injection site. Understanding this could help refine protocols for other multi-dose vaccines.”

The immune response to vaccines primarily begins in the lymph nodes nearest to the injection site. Typically, adult and adolescent vaccinations are administered intramuscularly in the upper arm, often the non-dominant arm. The study aimed to explore whether vaccinating in the same limb, and thereby utilizing the same lymph nodes, could optimize immune response.

Since directly assessing human lymphoid tissue during antibody development poses challenges, researchers conducted their study using a mouse model. Mice received two doses of a COVID-19 vaccine 14 days apart, with one group receiving both doses in the left hind leg and another receiving one dose in the left hind leg and the other in the right forearm. Their immune responses were measured on days 19 and 28 post-vaccination.

The findings also suggested that vaccination site influences immune cell response when using vaccines tailored for different COVID-19 variants. Administering variant vaccines in the same limb led to a broader initial antibody response, which could be particularly relevant as viruses continue to evolve. However, this did not impact long-term immunity.

The research team intends to further explore the mechanisms underlying the enhanced early immune response seen in same-arm vaccinations. “We are interested in determining whether this applies to other vaccines, investigating how timing between doses affects immune responses based on location, and exploring alternative vaccination sites like the lungs to assess their impact,” Dr. Tan stated.

These findings could lead to more effective vaccination protocols across various diseases, providing valuable insights for immunization strategies worldwide.

More information: Lauren Burmas et al, Modulation of germinal center and antibody dynamics via ipsilateral versus contralateral immunization against SARS-CoV-2, The Journal of Immunology (2025). DOI: 10.1093/jimmun/vkae067

Journal information: Journal of Immunology

Disclaimer: This article summarizes scientific research and is intended for informational purposes only. Readers should consult healthcare professionals for medical advice regarding vaccinations and immunization strategies.

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