Health and Medicine
PUBLISHED
Here’s a little experiment for you: ask a few friends and family members about their experience of getting their last flu shot or COVID booster. Chances are you’ll get a rough split between the “I had a headache and couldn’t lift my arm for days” people and the “didn’t feel a thing and ran a half-marathon the next day” people.
But why is that? What determines who gets side effects from vaccination and who doesn’t?
We’re mainly talking about mild, temporary effects here, things like feeling briefly feverish or having a red, swollen arm for a few days. In a new study, scientists believe they’ve uncovered factors in the human immune system that make these side effects more likely to occur.
Understanding vaccine reactions
Some trends in who gets these symptoms had already been observed, such as the fact that older adults tend to experience fewer of these temporary effects.
There's also been some research to suggest that the nocebo effect – the opposite of the placebo, where belief that something will cause negative effects makes those effects stronger or more likely to occur – can explain some vaccine side effects.
But at least some of the time, there's definitely something biological going on.
“Whilst we know that older people tend to experience fewer reactions to vaccination because of age-related declines in immune function, and that the vaccine dose can influence the severity of side effects, the biological mechanisms underlying these individual differences in symptoms have remained poorly understood,” said senior author Arnaud Didierlaurent, an associate professor at the University of Geneva, in a statement.
It’s important to understand this better, the team says, because the potential for a reaction is one of the reasons why some people may be hesitant to get a vaccine.
The team began their research in 2021, zeroing in on the COVID-19 mRNA vaccines and studying 51 otherwise healthy people who got either Moderna’s SPIKEVAX or Pfizer-BioNTech’s COMINARTY.
The participants were monitored for seven days to pick up any vaccine reactions they experienced. These commonly included pain at the injection site, fever, muscle aches, and fatigue, and the reactions tended to be more frequent after the second vaccine dose, as has been observed previously.
Blood tests revealed a link between the vaccine reactions and an innate immune antiviral defense system called interferon.
Choose your fighter
Interferons are substances produced naturally by the body in response to disease that influence the response of the immune system. There are three main types: alpha, beta, and gamma. They’re part of a larger family of proteins called cytokines.
Higher levels of interferons have previously been associated with long COVID and other autoimmune conditions because they contribute to a generally inflammatory environment within the body. When you’re trying to fight off a virus, that’s exactly what you want, but you can have too much of a good thing.
“This innate immune defence system helps us, in particular, to fight viral infections. The more active a person’s natural interferon response is, even before vaccination, the more pronounced their reactions to vaccination are likely to be,” said first author Natacha Madelon.
“For reasons we do not yet fully understand – but which may be linked to genetic factors, a particular microbiome or a previous inflammatory episode – some individuals have a stronger interferon-related immune signature before receiving the vaccine,” added Didierlaurent, “which appears to influence how strongly they react to vaccination.”
Of mice and monocytes
Another interesting mechanism emerged from separate experiments in mice, which may help explain why vaccine reactions are known to happen more frequently after a second dose.
The whole point of a vaccine is to prompt the immune system into mounting a specific defense against a virus. To achieve this, most vaccines contain a key ingredient called an antigen – sometimes it can be a whole virus particle, sometimes just fragments of protein – that gives the immune system a heads-up to watch out for the real virus.
In the case of mRNA vaccines, the process is a bit more convoluted – or, as we prefer to look at it, elegant and fascinating – as rather than containing an antigen, the vaccines contain a blueprint that lets your cells produce their own. So the process is a little different, but the end result is the same.
According to the team’s findings, however, the very fact vaccines promote this adaptive immune response means a stronger reaction – and stronger side effects – are more likely after a second dose.
In their mouse model, the researchers observed that white blood cells called monocytes were more strongly activated and recruited to the vaccination site after the second dose, leading to inflammation that could manifest as things like redness and pain.
This mechanism, the team stressed, will need to be validated in human studies before we’ll know for sure if it’s a factor. It's also worth noting that, for some vaccines, multiple doses are essential to build up enough immunity to actually protect you from illness.
No reaction? No problem!
In the statement published alongside these reults, Didierlaurent also addressed a persistent myth about vaccination – one I heard all the way back when I was a teenager getting my BCG shot and that has stuck around ever since.
“In any case, a mild reaction, or even the absence of symptoms following vaccination, does not in any way mean that the vaccine is ineffective,” he said. “The severity of side effects is therefore not, in itself, an indicator of how well a vaccine is working.”
So if you’re among the lucky majority who don’t get any aftereffects from your vaccines this winter, that’s nothing to worry about. Rejoice in your pain-free arm and don’t assume that means you’re unprotected.
The study is published in Science Translational Medicine.
