Some people seem to sail through vaccination day with little more than a sore arm. Others spend the next 24 to 48 hours dealing with fever, chills, fatigue, headache, muscle aches or a general sense of being unwell.
New research suggests the difference may be rooted in one’s immune system’s activity even before the vaccine is given.
“According to the researchers, participants with a more active natural interferon response before vaccination were more likely to report stronger temporary reactions afterwards”
The study, led by a team of scientists at the University of Geneva and Geneva University Hospitals in Switzerland, examined why vaccine reactions vary so widely between people.
Published in Science Translational Medicine, the research focused on COVID-19 mRNA vaccines and found that a person’s baseline antiviral immune activity may help shape the intensity of their short-term symptoms after vaccination.
The findings do not suggest that common vaccine side effects are dangerous, nor do they show that people with stronger symptoms gain greater protection. Instead, they offer a possible biological explanation for an experience that has long puzzled patients and clinicians alike: why one person feels almost nothing after a vaccine while another needs a quiet day in bed.
For most people, vaccine reactions are absent or mild. A painful arm, tiredness, headache, low-grade fever or aches are familiar examples. These effects usually resolve within a few days.
They are signs that the body has noticed the vaccine and has begun mounting an immune response. They should not be confused with rare serious complications, which require separate clinical assessment.
“It suggests that pre-existing differences in the immune system’s antiviral readiness may influence how intensely the body reacts to the vaccine itself”
The Swiss team enrolled 51 healthy adults, with a median age of 43.5 years, who received two doses of a COVID-19 mRNA vaccine. Participants were monitored closely for a week after each dose. Researchers recorded symptoms, then compared those reports with detailed measurements of the participants’ immune responses.
Their central finding involved interferons, a group of signalling proteins that play a crucial part in the body’s early response to viral threats. When cells detect signs of a virus, they can release interferons. These proteins act as an alarm system. They help neighbouring cells prepare their defences and influence the wider immune response.
Not everyone has the same level of interferon-related activity at baseline. According to the researchers, participants with a more active natural interferon response before vaccination were more likely to report stronger temporary reactions afterwards.
This is an important distinction. The study does not say that people with more side effects have a superior immune system. It does not establish that stronger reactions result in better protection against infection or severe disease. Rather, it suggests that pre-existing differences in the immune system’s antiviral readiness may influence how intensely the body reacts to the vaccine itself.
“Experts caution that this is still an early area of research. The study was relatively small, involving 51 healthy adults, and it centred on COVID-19 mRNA vaccination”
The work also looked beyond the human volunteers. Scientists used mouse models to examine what might happen within the immune system after repeated exposure to an mRNA vaccine.
After the first dose, the mice developed antibodies and trained T cells, two core components of adaptive immunity. Antibodies can recognise and help neutralise pathogens. T cells support the immune response in several ways, including helping to identify infected cells.
After the second dose, however, the researchers observed a faster and stronger response from monocytes. Monocytes are white blood cells that form part of the innate immune system, the body’s rapid first line of defence. This response may be amplified by the immune memory established after the first dose.
In practical terms, the second injection may trigger a swifter inflammatory response in some people, contributing to short-lived symptoms such as fever, fatigue and body aches.
That pattern is familiar to many people who received two-dose COVID-19 vaccines. Some reported more noticeable short term side effects after the second injection than after the first. The new study offers a possible explanation, although it cannot account for every individual experience.
Age is already known to affect vaccine reactions. Older adults often report fewer short-term symptoms after vaccination, partly because immune responses can become less vigorous with age. Vaccine dose also matters. Different vaccine platforms, doses and intervals between doses may influence the nature and frequency of side effects.
The latest research adds another layer, an individual’s immune state before vaccination may also be relevant.
Experts caution that this is still an early area of research. The study was relatively small, involving 51 healthy adults, and it centred on COVID-19 mRNA vaccination.
Its findings should not automatically be extended to influenza vaccines, RSV vaccines or other routine immunisations. Scientists are still investigating whether similar interferon-linked mechanisms influence responses to other vaccines.
There may be many reasons why interferon activity differs from one person to another. Genetics could play a role. So could previous infections, ongoing inflammation, sleep, stress, age, certain medicines and the composition of the gut microbiome.
The microbiome refers to the community of microorganisms living in and on the body, especially in the digestive system. It is increasingly recognised as an influence on immune function, though the precise relationship between the microbiome and vaccine side effects remains uncertain.
This complexity means there is no practical screening test that can currently predict who will feel unwell after a vaccination. Nor is there an established method for preventing ordinary, temporary post-vaccination symptoms by changing a person’s immune response beforehand.
For patients, the immediate message remains straightforward. Mild reactions are common and usually settle quickly. Rest, fluids and simple symptom relief measures may help. Paracetamol can be used where appropriate, following the advice on the packet or guidance from a pharmacist or clinician.
People should seek medical advice if symptoms are severe, persistent, unusual or worrying.
Urgent medical assessment is appropriate for symptoms that could indicate a serious allergic reaction. These include difficulty breathing, swelling of the face or throat, widespread hives, severe dizziness or collapse. Such reactions are rare, yet anyone who has previously had a severe allergic reaction to a vaccine or one of its ingredients should speak with a healthcare professional before receiving further doses.
The new findings may also help address a common misconception: more side effects do not mean a vaccine is “working better”. Immune protection is not measured by how ill someone feels the next day.
A person can have a robust and useful immune response with few or no noticeable symptoms. Equally, someone who has fever and fatigue may simply have a more active inflammatory response, not necessarily a stronger level of lasting protection.
That reassurance matters. Vaccine side effects can be unpleasant, especially for people balancing work, caring responsibilities or existing health problems. Yet the symptoms generally reflect transient immune activation, not infection with the disease the vaccine is designed to prevent. COVID-19 mRNA vaccines do not contain live SARS-CoV-2 virus, so they cannot cause COVID-19.
The research is also a reminder that vaccination is not an identical biological event for every person. A vaccine dose may be standardised, but the immune systems receiving it are not. They have different histories. They carry the effects of age, previous infections, inherited biology and environmental exposures. This variation can make some people more prone to short-lived reactions.
Understanding those differences could eventually support more personalised approaches to vaccination. Researchers may one day be able to identify biological markers linked to reactogenicity, the medical term for predictable short-term reactions such as fever, aches and injection-site pain. That knowledge could improve vaccine design, dosing strategies or counselling for people concerned about side effects.
For now, the evidence supports a more modest conclusion. Short-term vaccine reactions appear to be influenced, at least in part, by the way an individual’s innate immune system is primed before vaccination. Interferon-related activity is one promising piece of that puzzle.
The researchers’ work offers a useful scientific explanation without changing current vaccine guidance. Most people can expect no symptoms or mild effects that improve within a few days.
Stronger temporary symptoms can occur. They are not generally a reason to avoid vaccination, and they do not indicate that the vaccine has caused the illness it is intended to prevent.
Seasonal vaccines remain an important public health tool, particularly for people at higher risk of severe illness. That includes older adults, pregnant people, those with certain long-term medical conditions, and individuals with weakened immune systems.
Recommendations differ by country, age group, health status and vaccine availability. People with questions about eligibility, timing or previous reactions should consult a GP, pharmacist or local public health service.
The study from Geneva does not eliminate uncertainty around vaccine reactions. It does, however, move the discussion beyond anecdote. Rather than treating side effects as random or mysterious, it points towards measurable differences in antiviral immune signalling.
For people who have wondered why they react more strongly than friends or family members, that may provide a clearer answer: the body’s alarm system may simply be set to respond more quickly.
The post Scientists Found Possible Reasons Why Some People Have Worse Vaccine Side Effects first appeared on PP Health Malaysia.
