It’s normal to feel a bit lousy in the day or two after your COVID-19 jab – in fact, it can be helpful to think of it as a positive sign.
Experts say mild side-effects such as tiredness, fevers, muscle aches, and arm pain are “normal signs your body is building protection”.
But if feeling rubbish offers some reassurance that the vaccine is working, what does it mean if you don’t have symptoms after the jab?
Thankfully, it’s nothing to worry about: an absence of symptoms is not a sign the vaccine isn’t doing its job, according to research published this week in JAMA Internal Medicine.
It suggests people who don’t experience any side-effects from mRNA COVID-19 vaccines still produce a robust antibody response.
US researchers measured the antibody levels of almost 1000 healthcare workers two weeks after their second dose of the Pfizer or Moderna vaccine, and asked them to report any side-effects.
They found almost 100 per cent of vaccine recipients “mounted a strong antibody response to the spike protein … independent of vaccine-induced reactions”.
The findings echo what clinical trials show: COVID-19 vaccines are highly effective irrespective of age, sex, or the presence of side-effects.
So why do vaccines leave some of us feeling worse than others? And how exactly does our body mount an immune response?
How do vaccines mimic a virus?
In order to train our bodies to recognise pathogens (and fight them off down the track), vaccines introduce our immune system to part of a pathogen – known as an “antigen” – which triggers an immune response.
This antigen might be a weakened or inactivated virus, or it might be just one part of a pathogen – for example, the spike protein found on the surface of SARS-CoV-2 (used by the virus to latch onto and enter human cells).
Traditional vaccines, including some COVID-19 jabs, deliver antigens directly to the body.
But other COVID-19 vaccines, such as the Pfizer, Moderna and AstraZeneca jabs, use different technology.
Instead of delivering the antigen itself, the vaccines contain a genetic blueprint (or set of instructions) that tell the body to make the SARS-CoV-2 spike protein using the body’s own cells.
To do this, the Pfizer and Moderna jabs contain a single strand of genetic material – that’s the mRNA or messenger RNA – which is encapsulated in a protective fatty coating.
The AstraZeneca vaccine, on the other hand, contains double-stranded DNA, which is carried into the body via a weakened version of a common cold virus, engineered so it doesn’t replicate.
“The DNA gets taken up by your cells, that DNA then encodes the mRNA, and then it turns into a protein … which is what your body is going to respond to,” says Stuart Tangye, an immunologist from the Garvan Institute of Medical Research.
“The mRNA vaccine just skips that first step.”
What happens in your body as soon as the jab hits your arm?
When the vaccine is first injected into your arm, the mRNA or DNA it contains is taken into your cells, which “read” the genetic material and begin to build antigens.
“Our muscle cells start making the spike protein, and it gets expressed on the surface of the muscle cell … because that’s where we’re getting injected,” Professor Tangye says.
As this is happening, your body’s first line of defence against invading pathogens – the innate immune system – is already kicking into gear, University of Queensland immunologist Larisa Labzin says.
“Our innate immune system has got these receptors that are really good at detecting bits of viruses and bacteria, or any sign of cellular damage.
“So when we get that needle in our arm … that mRNA and DNA tricks the innate immune system into thinking it’s seeing a virus.”
Two key types of white blood cells arrive on the scene: macrophages and dendritic cells, which help to screen the blood, tissues and organs for suspicious signs.
“They survey the body … looking for junk and other stuff that shouldn’t be there,” Professor Tangye says.
As they circulate, macrophages eat up dead cells (and in the case of infection, destroy foreign cells), while dendritic cells start to collect samples of the antigen that’s been introduced – to help inform the body’s adaptive immune response (more on that later).
When the cells sense there is a problem, they call for backup: triggering the release of a group of proteins called cytokines, which help signal other immune cells to the injection site.
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These include neutrophils, the most abundant type of white blood cell, and natural killer cells, which patrol the blood and lymphatic system looking for abnormal cells.
Your immune reaction kicks in
This innate immune response typically unfolds over the course of a few hours to several days, and can sometimes result in flu-like symptoms such as a high temperature, or swelling at the injection site in the arm.
These processes are designed to aid your immune response, and are a healthy sign your immune system is working.
“All those cytokines act on your blood vessels to make them wider so more blood can flow to that [injection] area, so it can deliver more of those immune cells to that site,” Dr Labzin says.
“That’s why your arm swells and why it gets painful.”
If the inflammatory signal is strong enough, the immune system may trigger a large, systematic response, such as a fever.
That’s because a warmer body makes it harder for bacteria and viruses to reproduce.
“The innate immune system basically says, ‘This is too big for me to control, I need to notify the whole body of how serious this is’,” Dr Labzin says.
These symptoms usually subside within a day or two, because the body’s response to vaccination is “self-limiting”: it only makes as much spike protein as the genetic material in the vaccine allows.
“That’s the big difference between the vaccine and natural infection,” Dr Labzin says.
“With natural infection, the virus is going to keep replicating, and therefore the amount of [inflammatory] signal will grow exponentially.
“But with the vaccine, you’re just getting one dose – so you’ll get the pulse of that signal, but then it drops off.”
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Then antibodies start to appear
The genetic material in the vaccine is quickly used up – but not before the dendritic cells (the ones that help to identify the foreign antigen) have had a chance to take the information they’ve collected to the engine room of the immune response: the lymph nodes.
“The cells go into the draining lymph node, which would be under your arm,” Professor Tangye says.
This next part of the process is known as the adaptive immune response. It’s where B-cells and T-cells (categorised as helper T-cells and killer T-cells) are triggered into action.
“The T cells and B cells are really fundamental,” Professor Tangye says.
“This is when [the immune response] really starts becoming specialised to respond to just that [antigen].”
Armed with more information about the threat at hand, killer T-cells go in search of infected cells and swiftly destroy them, says Nobel laureate Peter Doherty.
“The killer T-cells go round the body, find the virus-infected cells, which are making new virus particles, and bump them off,” says Professor Doherty, who won a Nobel prize for discovering exactly how this process works.
“They’re the hitman of immunity.”
Meanwhile, B-cells produce special proteins called antibodies that latch onto antigens like a lock and key. By binding to the spike protein, they effectively neutralise the virus – and stop it from infecting new cells.
Helper T-cells, as the name suggests, provide assistance to B-cells (ensuring they make the most effective antibodies) and help the body to recruit more immune cells as needed.
“We need helper T-cell responses to make the antibody response good and help drive the multiplication of those B-cells,” Professor Doherty says.
It typically takes a week or two for antibodies to appear.
Once the immune system is confident the threat has been neutralised, most of these B-cells and T-cells disappear. But a subset of antibodies and “memory cells” stick around.
It’s these cells that ultimately provide us with long-term immunity, and protect us in case we encounter the same threat again.
“These T cells and B cells remember the virus – via the spike protein – so if we do get infected, the response is very quick,” Professor Tangye says.
“Our immune system is revved up and ready to go.”
Why is the second jab essential?
The first dose of the COVID-19 vaccine primes our immune system against SARS-CoV-2, but it’s the second dose that really fortifies our response, Dr Labzin says.
“Like most things, the first draft we do might not be very good.
“But the more times we have to edit and improve it, the better it gets. And it’s the same for our B-cells and T-cells.”
The second jab prompts the immune system to ramp up the quality of antibodies and T-cells, so the adaptive immune response is as targeted as possible.
It also gives antibody levels an extra “kick-along”, Professor Tangye says, so our immune response is faster and stronger if we face the virus again.
“In your blood you’ve got levels of antibodies, and depending on what the pathogen is, they have to be at a particular level to be effective.
“What the second shot is doing is really just kicking that up.”
Why do different people have different symptoms?
It’s not clear why COVID-19 vaccines knock some people around more than others, but data suggests younger people, women, and those who previously had a COVID-19 infection are more likely to report side-effects.
Experts say younger people have more robust immune systems, which may explain why they have stronger responses to the vaccine.
When it comes to the strength of immunity we generate, Dr Labzin says our genetics and overall health can also play a role.
“Things like obesity and diabetes can definitely impact on your immune response, and tend to give you a weaker antibody and T-cell response.
“Your genetics will also play a part. You might be better or worse at making those innate cytokines.”
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