When it comes to getting the most out of a vaccine, arm consistency can make a difference. Some studies suggest that getting a booster in the same arm as the initial shot can boost the immune system’s response. Now, we’re getting clues as to why using the same arm for initial and booster doses might be better for activating the immune system’s response to a vaccine.
In a small study published April 28 in the journal Cell, researchers from Australia found that when a vaccine is given, specialized immune cells called macrophages prepare to fight inside lymph nodes. The macrophages then direct where memory B cells go to more effectively respond to the booster when it is given in the same arm.
According to the team, the findings were made in mice and validated in human participants and offer enough evidence to refine how we approach vaccines.
“A unique and elegant aspect of this study is the team’s ability to understand the rapid generation of effective vaccine responses,” Anthony Kelleher, a study co-author and clinician scientist at the Garvan Institute of Medical Research and the Kirby Institute at University of New South Wales Sydney, said in a statement. “We did this by dissecting the complex biology in mice and then showed similar findings in humans. All this was done at the site of the generation of the vaccine response, the lymph node.”
[ Related: New study: US could see millions of measles cases if vaccination rates keep dropping. ]
Matters of site
During immunization, a harmless version of a pathogen called a vaccine antigen is introduced into the body. The antigen is then filtered through the lymph nodes. These work like immune system boot camps that train the body to fight off the real pathogen when and if they are confronted with it.
Previously, the team from the study looked at memory B cells. These cells are crucial for generating antibody responses when infections return. They found that memory B cells tend to stay on the lymph node closest to the injection site. They migrate to the outer layer of the local lymph node and interact closely with the macrophages–those specialized immune cells primed for battle in the lymph nodes–that reside there. When a booster was given in the same location, those already-on-alert macrophages captured the antigen and activated the memory B cells more efficiently. In turn, this made high quality antibodies.
“Macrophages are known to gobble up pathogens and clear away dead cells, but our research suggests the ones in the lymph nodes closest to the injection site also play a central role in orchestrating an effective vaccine response the next time around. So location does matter,” study co-author and immunologist Rama Dhenni said in a statement.
Activating antibodies
In this new study, the team conducted a clinical study with 30 volunteers receiving the Pfizer-BioNTech COVID-19 mRNA vaccine. Ten of the participants received their booster dose in the same arm as their first dose. The other 10 were given the second shot in the opposite arm.
According to the results, the group who received both doses in the same arm began producing neutralizing antibodies against the virus within the first week after the second dose. They also showed to be more effective against the potent Delta and Omicron COVID-19 variants. After four weeks, both groups had similar antibody levels. However, that early protection could be important during an outbreak.
“If you’ve had your COVID jabs in different arms, don’t worry – our research shows that over time the difference in protection diminishes,” study co-author and immunologist Mee Ling Munier said in a statement. “But during a pandemic, those first weeks of protection could make an enormous difference at a population level. The same-arm strategy could help achieve herd immunity faster – particularly important for rapidly mutating viruses where speed of response matters.”
Nature’s ‘brilliant system’
It’s important to note that this study included a small sample size and other studies have found benefits in switching arms. In future research, the team hopes to build on this work to refine vaccination guidelines and enhance the effectiveness of vaccines.
“If we can understand how to replicate or enhance the interactions between memory B cells and these macrophages, we may be able to design next-generation vaccines that require fewer boosters,” Tri Phan, a study co-author and clinical immunologist, said in a statement. “This is a fundamental discovery in how the immune system organises itself to respond better to external threats – nature has come up with this brilliant system and we’re just now beginning to understand it.”
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