• A new study explored whether alternating arms for multidose vaccines could improve immunity.
  • Examples of multidose vaccinations include those for COVID-19, measles mumps and rubella (MMR), and shingles.
  • Multidose vaccinations can be received in the same or different injection site for each dose.
  • Researchers say that switching arms for the initial and booster doses of mRNA COVID-19 vaccines helped improve subjects’ immune response and vaccine effectiveness.

The COVID-19 vaccine is still relatively new, and researchers are still interested in studying how to maximize its effectiveness.

Typically, people receive the COVID-19 vaccine in the upper arm, which has multidose options. Multidose vaccines can be received in the same or different injection site for each dose. Other examples of multidose vaccines include those for measles mumps and rubella (MMR) and shingles.

A recent study published in The Journal of Clinical Investigation examined whether switching arms for two doses of the Pfizer BioNTech COVID-19 vaccine increased effectiveness.

Participants who switched arms for vaccine doses experienced a higher antibody response than those who received doses in the same arm.

The results showed this response increased over time in the subsequent follow-up visits.

These results point to a simple way to increase vaccine effectiveness. Future research could explore whether switching injection sites for other multidose vaccines could help improve immunity.

COVID-19 vaccination has effectively slowed infection rates and helped reduced severe illness.

The two main COVID-19 vaccines are both mRNA vaccines produced by Pfizer and Moderna.

Current recommendations from the Centers for Disease Control and Prevention (CDC) involve single doses of the Moderna or Pfizer-BioNTech vaccines for people who are not immunocompromised. However, multiple doses are still recommended for people who are immunocompromised.

Previously, other individuals received two doses of the Pfizer-BioNTech vaccine. Researchers of the current study wanted to see if the immune response produced by the Pfizer-BioNTech vaccine differed based on whether or not participants received doses in the same arm or the opposite arm from their initial dose. Study authors note there hasn’t been a lot of research conducted in this area.

Researchers included participants from the OHSU COVID-19 Serology study, including almost 950 adults in their analysis. A total of 507 participants received at least two doses in the same arm, and 440 received at least two doses in opposite arms.

Researchers also looked at antibody response in a subgroup of matched pairs, with each pair having similar age, gender, vaccination, and time intervals between blood sample testing.

They were able to follow up on immune response among participants for up to 14 months after boosting.

Overall, researchers found that the group receiving vaccination doses one and two in opposite arms had a better immune response than those receiving doses in the same arm.

They saw higher levels of SARS-CoV-2 specific serum antibodies. They observed this difference more with later immunity testing than with earlier testing.

Study author Dr. Marcel E. Curlin, associate professor of medicine in the division of infectious diseases at the Oregon Health and Sciences University and the medical director for occupational health at OHSU, noted the following to Medical News Today:

“In the context of first-time receipt of a 2-dose vaccine regimen, antigen–specific antibody levels resulting from vaccination are higher when giving the second dose in the contralateral arm relative to the first dose. This effect is durable, lasting more than a year after boosting. Contralateral vaccination also results in a “broader” immune response to challenges slightly different from the original vaccine (for example, to a variant of the original virus). We do not yet understand why this happens, but it is likely related to formation of memory and multiple rather than individual lymphoid centers.”

Non-study author Dr. Arturo Casadevall, PhD, a microbiology and immunology expert with Johns Hopkins Medicine, told MNT the study data are strong.

“The finding that contralateral arm vaccination results in higher antibody responses suggests that the simple intervention of switching arms during initial vaccination and boosting could produce stronger immunity and perhaps longer lasting protection,” he shared.

“This is an example of simple medical research with potentially high benefits for the individual and for public health.”

Despite the promising implications the new research does have certain limitations.

First, researchers acknowledge the potential bias that could have occurred, though they believe this cannot account for all the results seen. Second, this study looked at a specific type of vaccination among adults and did not examine alternative immunization routes, so the results may not apply or be significant for other areas.

Researchers also did not look at cellular immunity when looking at potential protection from severe illness.

In addition, the cohort was comprised of healthcare workers, a specific population, so more research could also include more individuals in other fields.

Only 23% of participants were male, so it’s also possible for future research to include more gender balance. There was also a limitation based on how many participants completed all follow-up appointments.

Non-study author Jessica Smith Schwind, PhD, MPH, director at the Institute for Health Logistics & Analytics and associate professor of Epidemiology, Georgia Southern University, said from an epidemiologic perspective, the study has the potential to influence standard practice, but shared a word of caution:

“However, a randomized study will be the gold standard to determine if a contralateral administration of the vaccine series would be most beneficial (and to what extent) for mRNA COVID-19 vaccinations. Also, it is important to keep in mind that immunologic response is a multi-faceted, complex process that can be measured in different ways. This study only measured antibody titers, which is only one component that influences a person’s overall immune response to a pathogen.”

Future research could focus on verifying these initial findings and expanding the data collection, such as looking at additional time points after vaccination.

At a basic science level the observation raises new questions for immunological research since it is difficult to explain how this effect occurs based on current understanding of how immune responses develop,” Dr. Casadevall said.

“I think the next step would be to carry out a prospective randomized controlled trial to determine if the effect holds. If the findings are replicated, I can imagine that this could lead to changes in clinical practice for how vaccines are administered and would stimulate new basic science research to understand the immunological mechanisms involved,” Dr. Casadevall noted.

This research opens the door for future research into maximizing vaccine effectiveness.

“We can probably derive greater levels of protection elicited by vaccines, based on the way we provide vaccination,” Prof. Curlin noted.

“Improved protection would likely be in the form of some degree of decrease in disease severity, particularly those with comorbid illness who are likely susceptible to severe disease.”

One area for future research is looking into how switching vaccination sites may apply to other multidose vaccines. For example, the boost in immunity seen in this study may hold true for other multidose vaccines and increase their overall effectiveness.

Researchers note that future research can include pediatric data, as many of these multidose vaccines are usually part of child vaccination regimens.

Professor Curlin noted the potential benefits of this line of research in the future:

“This effect, if generalized, could change the way we administer certain vaccine regimens, particularly in children. This effect could [also] have an impact on vaccines in development, particularly those with efficacy near threshold cutoffs for viable vaccine products. [However], it is important to remember that this issue requires additional study to help us better understand the mechanism for this effect and its generalizability to other vaccines.”

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