The simplicity of solutions can sometimes be overlooked amidst scientific advancements. For over two centuries, researchers have explored various methods of vaccination, including different dosages, vaccine agents, and forms of administration, to prepare the immune system for an eventual attack using weakened pathogens or parts thereof. However, very few experts have investigated whether the arm receiving the vaccine makes a difference. Researchers at Oregon Health & Science University (OHSU) suspect that it may be significant. The query arose during the early days of the COVID-19 pandemic when healthcare workers participating in vaccine response studies asked OHSU experts whether they should alternate arms between the first and second jab. The team was unsure of the advice to give since most scientists had previously assumed that arm selection didn’t matter.

“This question hasn’t really been extensively studied, so we decided to check it out,” says infectious disease specialist Marcel Curlin.

Curlin and his colleagues had difficulty finding information on the topic as they only came across four papers in the scientific literature, with mixed results.

In one randomized controlled trial among infants, it was found that giving influenza vaccinations in different arms at 2, 3, and 4 months of age resulted in higher antibody levels as compared to when they were given in the same arm.

A newer study conducted in 2023, however, found that immune responses were higher when COVID-19 vaccinations were given in the same arm as compared to different arms.

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To obtain a clearer understanding of the matter, researchers at OHSU conducted tests on 947 participants who received a two-dose COVID-19 vaccination.

Half of the group was randomly selected to receive the second dose in the same arm as the first one, while the other half received the staggered jabs in different arms. After four weeks of receiving their second dose, SARS-CoV-2-specific serum antibodies were found to be 1.4 times higher in those who received the vaccine in different arms.

A subset of 108 people in 54 pairs were matched based on their gender, age, and time of vaccinations, and their blood work was compared.

Serum samples collected in the weeks and months after vaccination showed clear differences between the groups. Those who received shots in both arms had up to a four-fold increase in SARS-CoV-2-specific serum antibodies four weeks after the second jab when compared to those who received shots in just one arm.

Furthermore, this improved immune response lasted for more than a year after the booster was administered.

“It turned out to be one of the more significant things we’ve found, and it’s probably not limited to just COVID vaccines,” Curlin hypothesizes.
“We may be seeing an important immunologic function.”

Curlin and his colleagues are currently unsure about the special function and workings of it, but they have some ideas.

It is a common practice to administer vaccines without considering the previous site of vaccination. However, it is important to note that this factor can significantly affect the immune responses that occur later. When a vaccine is administered in muscle, the immune cells recognize the antigens in the vaccine, which detain the invaders and take them to the lymph nodes for further investigation. This process prepares the immune system against this specific antigen by sending out wanted signals of the invader.

Since different areas of the body drain to distinct lymph nodes, by inducing an immune response on both sides, the body may be more vigilant.

“By switching arms, you basically have memory formation in two locations instead of one,” explains Curlin.

The study conducted in 2023 yielded results that were opposite to the current findings. According to the previous study, vaccinations given in the same arm were found to be more effective in preparing the immune system against COVID-19. It is possible that the difference in results could be attributed to the timing of blood serum tests.

The earlier study conducted blood serum tests only two weeks after administering the vaccinations. It is important to note that the immune cells responsible for remembering the characteristics of an antigen continue to mature and increase in number for several months following vaccination.

It was only at the three-week mark that researchers at OHSU observed that vaccinations given in both arms began to produce better results than those given in the same arm. Moreover, these benefits continued to improve gradually, reaching their peak during the fourth week and lasting for several months thereafter.

Although more research is required to determine the advantages and disadvantages of vaccinating different arms, Curlin says he is willing to switch things up for his next booster shot.

This news is a creative derivative product from articles published in famous peer-reviewed journals and Govt reports:

1. Fazli, Sedigheh, et al. “Contralateral second dose improves antibody responses to a two-dose mRNA vaccination regimen.” The Journal of Clinical Investigation (2024).
2. Organization WH. WHO Coronavirus (COVID-19) Dashboard. september-2022. Updated 30 June 2023 Accessed 8 July 2023, 2023.
3. Moodie Z, Dintwe O, Sawant S, Grove D, Huang Y, Janes H, et al. Analysis of the HIV Vaccine Trials Network 702 Phase 2b-3 HIV-1 Vaccine Trial in South Africa Assessing RV144 Antibody and T-Cell Correlates of HIV-1 Acquisition Risk. The Journal of infectious diseases. 2022;226(2):246-57.
4. Tait DR, Hatherill M, Van Der Meeren O, Ginsberg AM, Van Brakel E, Salaun B, et al. Final Analysis of a Trial of M72/AS01(E) Vaccine to Prevent Tuberculosis. The New England journal of medicine. 2019;381(25):2429-39

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