More than a quarter of people injected with mRNA Covid jabs suffered an unintended immune response created by a glitch in the way the vaccine was read by the body, a study has found.
No adverse effects were created by the error, data show, but Cambridge scientists found such vaccines were not perfect and sometimes led to nonsense proteins being made instead of the desired Covid “spike”, which mimics infection and leads to antibody production.
mRNA jabs, such as the ones created by Moderna and Pfizer, use a string of genetic material to tell the body to create a specific protein that safely imitates an infection.
Research in the field, spanning decades, had been slow work. It often stalled because RNA itself is often attacked by the body as a foreign invader.
But in 2023, the Nobel Prize for Medicine went to the pair of scientists who had spent years working to fix the problem. It was done by taking one of the RNA bases, uridine, and swapping in a very similar synthetic alternative.
This breakthrough allowed scientists to create proteins in the body without the immune system attacking the jab.
It allows for quick and precise vaccines that are highly effective and was the backbone of the Covid vaccine response.
Not a perfect fit
It was thought the minor tweak to uridine caused no problems in cells, but a team of researchers at the University of Cambridge’s Medical Research Council (MRC) Toxicology Unit have now found when this partially synthetic code is read, the protein-making machine in the body sometimes struggles with the uridine analogues.Because it is not a perfect fit for what is expected, there can be a momentary pause which causes the process to stutter and a letter in the code can get skipped, much like a bike slipping a gear.
This process, called frameshifting, throws out the way the code is interpreted as it relies on groups of three bases, known as codons, being read in the right order.
This issue, caused by the jab’s code, throws the process completely out of sync and the entire subsequent code becomes garbled.
In the case of the Covid jabs, the end result is a nonsensical and harmless protein, the team found, which the body attacks and leads to an immune system flare-up. The new study, published in Nature, found this occurred in around 25-30 per cent of people.
Rogue protein fear
The vaccine is read well enough to create the strong protection against the coronavirus, the scientists say, but the frameshifting issue creates what was, until now, an unknown off-target effect.The code relating to the Covid vaccines was harmless and no issues were created. However the team say that subsequent mRNA vaccines used for other diseases or infections could, in theory, lead to viable proteins being created that are active in the body.
In this scenario not only is the vaccine not making the right protein, it could lead to a rogue protein being produced.
There is no evidence of this occurring in the Covid jabs, the authors stress, and they say any trials on other mRNA therapeutics would detect any such problems in early stages.
Dr James Thaventhiran, senior author of the report, said: “Research has shown beyond doubt that mRNA vaccination against COVID-19 is safe. Billions of doses of the Moderna and Pfizer mRNA vaccines have been safely delivered, saving lives worldwide.”
The authors also found that there is an easy way to eradicate the frameshifting events which relies on changing the code of the mRNA drug to minimise the use of the problematic pseudo-uridine.
Replacing it with a natural base that when read as a trio still makes the correct amino acid is enough to stop the unwanted skips and therefore improve safety without sacrificing efficacy.
These findings were shared with medicines regulator MHRA around a year ago, the scientists say, and updated vaccines that use the improved form of mRNA are in the works for cancer jabs, and other therapeutics.
‘Revolutionary technology’
“This technology is amazing and it’s going to be revolutionary as a new medicine platform for all sorts of things, but we’ve just made it a whole lot safer going forward,” Professor Anne Willis, co-senior study author and director of the MRC Toxicology Unit told reporters.“Ribosomes are somehow sensing the modified RNAs, but the Covid vaccines are very, very safe and very, very efficacious.
“But there are decoding issues with this technology that can cause stalling and frameshifting and we can get cellular immunity to these peptides after vaccination.”
However, she adds it is very exciting that there is a way to fix the issue, which “massively de-risks this platform going forward”.
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