Left arm or right? Why it matters where you get your vaccine

If you’re rolling up your sleeves for a flu or COVID vaccine this season, you may not give much thought to which arm ultimately receives the jab.

But new Australian research suggests location does matter when it comes to generating a strong immune response from booster vaccines.

Professor Tri Phan (left) and Dr Mee Ling Munier have made the discovery.Credit: Dominic Lorrimer

The study, published in the journal Cell on Tuesday, found booster vaccines given in the same arm as the first dose generated a stronger and more rapid immune response.

The findings, made in mice and replicated in humans, shed light on a previously understudied corner of the immune system, and could eventually be used to develop next-generation vaccines that require fewer boosters.

“This is a fundamental discovery in how the immune system organises itself to respond better to external threats,” said co-lead author Professor Tri Phan, director of the precision immunology program at the Garvan Institute of Medical Research.

What the study found

Vaccines work by introducing a harmless dose of a pathogen into the body, generating immune cells that remember the threat and can leap into action if and when it reappears.

Those immune cells spread throughout the body, providing widespread protection. But the study suggests the immune system also builds an additional layer of defence close to where a threat first appears (a vaccinated arm, for example).

Key to this response are immune cells called macrophages (meaning “big eaters” in Greek). These “housekeeper” cells lurk in the lining of our lymph nodes, devouring cellular debris and screening for anything suspicious – such as a familiar vaccine or virus – which they then capture and show to the memory B cells responsible for producing antibodies. (This response is what makes the lymph nodes swell when we’re ill or recently vaccinated).

Advanced intravital imaging shows memory B cells (red) interacting with macrophages (white) inside a lymph node (blue). Credit: Dr Rama Dhenni

Using high-definition biological imaging, Phan’s team discovered macrophages in lymph nodes near the site of the initial vaccination were “primed” to trigger a more effective and rapid antibody response than those found elsewhere in the body.

The results of the study contradict research published last year which suggested alternating arms may produce a more powerful immune response. Phan said that study showed antibody level peaked earlier when boosting on the same side – consistent with their own findings.

“When you actually look at it, it also shows very similar results to what we [found],” he said.

‘A really good opportunity’

While the theory showed promise in mice, COVID-19 gave researchers at the Kirby Institute an opportunity to observe the effectiveness of the Pfizer vaccine in 30 volunteers who had never contracted the virus.

“This kind of study is tricky in adults because most people have already been vaccinated or had some sort of infection,” said the Kirby Institute’s Dr Mee Ling Munier. “The rollout of the COVID vaccines was a really good opportunity.”

Those who received both doses in the same arm produced COVID antibodies within the first week after the second dose – significantly faster than when given in alternating arms. The antibodies were also more effective against the Delta and Omicron variants.

Although the gap narrowed within a month, the early boost can provide a crucial head start on rapidly mutating viruses such as COVID.

“During a pandemic, those first weeks of protection could make an enormous difference,” Munier said.

Munier and Phan said they would use the findings to investigate improved vaccines for viruses such as hepatitis and HIV, which are not guaranteed to produce antibodies in patients.

“If we can work out what makes these macrophages switch on … then we may also be able to come up with a strategy to make more effective vaccines,” said Phan.

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