Multiple Sclerosis vaccine

mRNA vaccine prevented multiple sclerosis in mice

Polina Loseva, N+1

The creators of the Pfizer anti-coronavirus vaccine tested the effect of the mRNA vaccine against multiple sclerosis on mice. By changing the RNA in such a way that it does not cause inflammation, but rather suppresses it, the researchers forced the immune cells of mice to become tolerant to the myelin protein. At the same time, they managed to stop the development of symptoms of the disease, and in some cases, even to restore the lost mobility of the tail to the animals.

The study was published in the journal Science (Krienke et al., A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis).

2020 was the year of the triumph of mRNA vaccines. If they did not go beyond the stage of clinical trials before, now at least two of them – from 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 of mRNA vaccines could be autoimmune diseases, for example, multiple sclerosis. This is an incurable disease, during which the target for the attack of immune cells becomes myelin – an insulating shell that oligodendrocyte cells build around neurons and their processes.

To prevent this attack, it is necessary to introduce lymphocytes to myelin antigens in advance – the idea is the same for all vaccines. However, unlike classical vaccinations, in the case of one's own antigen, this acquaintance should be carried out "in silence", outside the inflammatory context. Meeting with an antigen and 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, slows down.

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

Usually, nucleic acids that enter the bloodstream bind to TLR receptors on the cell surface (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, the receptors do not respond to RNA. The researchers injected mice with two versions of the vaccine – conventional or m1ψ – and confirmed that the concentration of pro-inflammatory proteins in the blood in the second case does not increase. This means that mRNA does not provoke inflammation and is suitable for causing anergy.

Then both versions 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 than usual T-regulatory cells that suppress the immune response.

However, this does not mean that mice have completely lost the ability to react to foreign proteins. The researchers verified that even after vaccination with m1ψ-mRNA, the immune system of 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 ordinary 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 pathology. If the disease managed to develop before the first stages, then vaccination significantly reduced its severity (p<0.05) and inhibited 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 the regeneration of nervous tissue.

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

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