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One in four people who received Moderna or Pfizer Covid vaccines experienced an unintended immune response

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More than a quarter of people given a Covid mRNA shot suffered an involuntary immune response created by a problem in the way the vaccine was read by the body, a study has found.

No adverse effects were created by the error, the data shows, but Cambridge scientists discovered that these vaccines were not perfect and sometimes led to the production of nonsense proteins instead of the desired Covid ‘spike’ , which mimics the infection and leads to the production of antibodies.

mRNA shots, such as those created by Moderna and Pfizer, use a string of genetic material to tell the body to create a specific protein that safely mimics an infection.

Research in this area, which has lasted decades, has been slow work. This often stagnates because the RNA itself is often attacked by the organism as a foreign invader.

But in 2023, the Nobel Prize in Medicine was awarded to two scientists who spent years working to solve the problem. This was achieved by taking one of the bases of RNA, uridine, and swapping it with a very similar synthetic alternative.

Pfizer and Moderna Covid vaccinesPfizer and Moderna Covid vaccines

Pfizer and Moderna Covid vaccines used mRNA technology – DAVID W CERNY/REUTERS

This breakthrough allowed scientists to create proteins in the body without the immune system attacking the vaccine.

It makes it possible to obtain rapid and precise, very effective vaccines and constitutes the backbone of the vaccine response against Covid.

The minor modification of uridine was thought to cause no problems in cells, but a team of researchers from the Medical Research Council (MRC) Toxicology Unit at the University of Cambridge discovered when this partially coded synthetic is read, that the protein production machine in the body sometimes struggles with uridine analogs.

Because it doesn’t perfectly match what is expected, there may be a momentary pause that causes the process to stutter and a letter of the code may be skipped, much like a bicycle slipping a gear.

This process, called frameshifting, changes the way the code is interpreted because it relies on groups of three bases, called codons, read in the correct order.

This problem, caused by the jab code, completely desynchronizes the process and all subsequent code becomes truncated.

In the case of Covid vaccines, the end result is a nonsensical, harmless protein, the team found, that the body attacks and leads to a surge in the immune system. The new study, published in Nature, found that this occurs in around 25 to 30 percent of people.

Fear of unwanted proteins

The vaccine reads well enough to create strong protection against the coronavirus, scientists say, but the frame-shifting problem creates what was, until now, an unknown off-target effect.

The code relating to Covid vaccines was innocuous and there were no problems. However, the team says that subsequent mRNA vaccines used for other diseases or infections could, in theory, lead to the creation of viable and active proteins in the body.

In this scenario, not only does the vaccine not produce the correct protein, but it could lead to the production of an unwanted protein.

There is no evidence that this happens in Covid vaccines, the authors point out, and they say that any trials of other mRNA therapies would detect such problems at an early stage.

Dr James Thaventhiran, lead author of the report, said: “Research has shown beyond doubt that the mRNA COVID-19 vaccination is safe. Billions of doses of the Moderna and Pfizer mRNA vaccines have been safely delivered, saving lives around the world.

The authors also discovered that there is a simple way to eradicate frameshift events that relies on modifying the mRNA drug code to minimize the use of the problematic pseudouridine.

Replacing it with a natural base which, read as a trio, still produces the right amino acid is enough to stop unwanted jumps and therefore improve safety without sacrificing effectiveness.

These results were shared with the medicines regulator MHRA about a year ago, the scientists say, and updated vaccines using the improved form of mRNA are in the works for cancer vaccines and other treatments .

“Revolutionary technology”

“This technology is incredible and it’s going to be revolutionary as a new medical platform for all kinds of things, but we’ve just made it much safer in the future,” Professor Anne Willis, director of the MRC toxicology unit.

“Ribosomes somehow detect modified RNAs, but Covid vaccines are very, very safe and very, very effective.

“But this technology has decoding issues that can cause hangs and frameshifts, and we may achieve cellular immunity to these peptides after vaccination.”

However, she adds that it is very exciting that there is a way to fix the problem, which “significantly reduces the risk for this platform in the future.”

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