mRNA vaccine prevents multiple sclerosis in mice

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The creators of the Pfizer anti-coronavirus vaccine have tested the effect of the mRNA vaccine against multiple sclerosis in mice. By altering the RNA so that it did not cause inflammation, but rather suppressed it, the researchers forced the immune cells of the mice to become tolerant to the myelin protein. At the same time, they managed to stop the development of the symptoms of the disease, and in some cases even return the tail mobility that was lost to the animals. Study published In the magazine Science.

2020 was the year of triumph for mRNA vaccines. If earlier they did not go beyond the stage of clinical trials, now at least two of them – from the companies Pfizer and Moderna – are already being used for mass vaccination against coronavirus. Probably, the success of these drugs will give an impetus to the development of the entire industry – and mRNA vaccines will be able to prevent other diseases, not necessarily infectious.

One of the areas of application for mRNA vaccines could be autoimmune diseases such as multiple sclerosis. It is an incurable disease in which myelin, the insulating membrane that oligodendrocyte cells build around neurons and their processes, becomes a target for the attack of immune cells.

To prevent this attack, lymphocytes need to be familiarized with myelin antigens in advance – the idea is the same for all vaccines. However, in contrast to classical vaccinations, in the case of one’s own antigen, this acquaintance must be carried out “in silence”, outside the inflammatory context. Meeting with an antigen, even in the absence of activation signals from neighbors, introduces lymphocytes into a state of anergy – that is, it does not mobilize, but on the contrary, inhibits.

According to this principle, they have already tried to create vaccines against multiple sclerosis – either the antigens themselves or the DNA encoding them were introduced into the blood. But these vaccinations were ineffective. Now the creator of the Pfizer anti-coronavirus vaccine, Ugur Sahin, and his colleagues at Johannes Gutenberg University and BioNTech have decided to test an mRNA vaccine against multiple sclerosis that encodes one of the regions of myelin protein.

Typically, nucleic acids that enter the bloodstream bind to TLRs on the surface of cells (the cells mistake them for viruses) and cause inflammation. To make mRNA non-immunogenic, the vaccine developers replaced all uridine nucleotides with 1-methylpseudouridine (m1ψ) – in this form, receptors do not react to RNA. The researchers injected mice with two variants of the vaccine – conventional or m1ψ – and confirmed that the concentration of pro-inflammatory proteins in the blood does not increase in the second case. This means that mRNA does not provoke inflammation and is suitable to induce anergy.

Then both variants of the vaccine were tested on model mice, prone to the development of autoimmune encephalomyelitis, an analogue of human multiple sclerosis. It turned out that under the influence of ordinary mRNA, the immune cells of the spleen do not lose their aggressiveness and continue to secrete pro-inflammatory proteins. But m1ψ caused a completely different reaction: in mice that got this option, even high concentrations of the antigen did not cause inflammation, but among the lymphocytes they found several times more normal T-regulatory cells that suppress the immune response.

However, this does not mean that mice have completely lost the ability to respond to foreign proteins. The researchers verified that even after vaccination with m1ψ-mRNA, the immune system of the animals reacted, for example, to the flu vaccine.

Finally, the authors of the work followed the development of the disease in control animals and those that received an injection of conventional or m1ψ-mRNA. In cases where mice received the vaccine at the very beginning of the disease, m1ψ-mRNA was able to completely stop the development of the pathology. If the disease had time to develop before the first stages, then vaccination significantly reduced its severity (p <0.05) and slowed down the deterioration. In some cases, the mice even got rid of tail paralysis – however, as the researchers note, this may be due to the anti-inflammatory effect of the vaccine, and not to the regeneration of nerve tissue.

Despite the fact that this vaccine has not yet been tried in humans, its creators believe that it could be successful. Among its advantages, they call the simplicity and low cost of creation. In addition, the simplicity of the design allows you to make it personalized – that is, injecting the patient with the mRNA of a specific protein to which an autoimmune response has occurred – or even combining several proteins in one vaccine.

We have already written about how scientists are trying to repair damaged neurons. via immune cells and plant extracts… And we told the story of the study of autoimmune diseases in the text “It’s autoimmune”.

Polina Loseva

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