RNA vaccines against Covid-19 are also in use. The researchers are now showing that such a vaccine could strengthen autoimmune diseases such as multiple sclerosis in the future. A broader application of the technology is also possible.
RNA vaccines protect against the infectious disease Covid-19 and are also tested against cancer. Researchers led by the Mainz doctor and Biontech founder Ugur Sahin are now showing that such active ingredients can also help with autoimmune diseases such as multiple sclerosis (MS). In one sample, the researchers write in the journal Science, they significantly improved the symptoms of an MS-like disease in mice.
An independent expert speaks of very exciting data, but urges caution. “You never know whether it works so well for humans,” says Ralf Gold, chairman of the medical advisory board of the German Multiple Sclerosis Society (DMSG).
Sahin said that the compatibility of this approach is currently being tested and that preparations are being made so that it can be researched in humans. Clinical trials could begin in about two to three years, “if everything goes according to plan”. In addition, RNA vaccines are being tested for other uses besides cancer, including chronic inflammatory diseases such as arthritis.
In December, BNT162b2, produced by Biontech against Covid-19, was the first RNA vaccine ever approved. This vaccine contains the pathogen’s genetic material, which the body then uses to make a viral protein. The aim is to activate the immune system so that in the event of an infection it will produce antibodies to intercept the Sars-CoV-2 virus.
The multiple sclerosis (MS) vaccine has a different purpose, in which the immune system damages the myelin that coats nerve fibers. Here a vaccine should ensure that the myelin is accepted by the body’s own defenses and does not produce any attacking immune cells or antibodies. In Germany, damage to the myelin sheath leads to motor problems such as paralysis, which affects over 250,000 people.
We were looking for a therapeutic approach that mimics the natural mechanisms of immune tolerance, ”write the researchers, most of whom work at the Mainz University Clinic. At the same time, the immune system should not be impaired by the RNA vaccination – for example when protecting against pathogens.
The RNA vaccine contains the blueprint (RNA) for the myelin oligodendrocyte glycoprotein (MOG) material – a part of the myelin sheath that is targeted by violent autoimmune reactions in MS. The vaccine is designed so that the protein is tolerated by the immune system. “With the RNA therapy approach, we induce the formation of immune cells that have a protective effect so that the tissue is not attacked,” explained Sahin.
The Mainz team tested the therapeutic effect in mice with experimental autoimmune encephalomyelitis (EAE). This disease, similar to multiple sclerosis, is based on inflammatory processes against components of the myelin. The vaccination increased the inflammatory responses in the mice and prevented the disease from progressing. At the same time, pathogens like the components of influenza viruses continued to react to the immune system.
The ability of the mice to build up a protective immune response and produce neutralizing antibodies was not affected. ”
In a further step, the researchers showed that additional immune cells against myelin were not triggered by the vaccination. This is important because this so-called bystander effect, in which the myelin sheaths are gradually attacked by other immune cells in a cascade, plays an important role in multiple sclerosis. Overall, the results lay the foundation for a later clinical application of the method in autoimmune diseases, according to the researchers.
DMSG expert Gold regards this transfer to humans as the crucial sticking point. “The study proves that the vaccination works excellently in mice,” says the director of the neurological clinic at the Ruhr University in Bochum. “But that is not easily transferable to humans.”
Again and again, active substances that have shown promise in animal experiments have failed in humans. On the one hand, this is due to the fact that the human immune system is very complex. On the other hand, humans are much more complex than the closely described strains of mice that are used in studies, says Gold.
Sahin is well aware of this problem. The method is now to be tested on various human immune cells in the laboratory, he says. Each person can have a different type of multiple sclerosis, he said, each with a specific pattern of autoimmunity. In the current study, the researchers succeeded in using a single antigen to induce tolerance in the immune system to all myelin tissue in mice, he said.