Spritzen sind eine mögliche Darreichungsform in der Behandlung der MS, neben Infusionen und Tabletten.

Vaccination Against Multiple Sclerosis (MS)

“What do you think, should I start MS treatment now or should I wait for the vaccination against MS?” asked me at the end of January 2021 a young MS patient who had sought me out for a second opinion. I had to orient myself briefly. I am constantly asked about vaccinations, but mainly in connection with COVID19. But no, the young woman actually approached me about a study on multiple sclerosis vaccination that had recently appeared in the renowned science magazine Science (Krienke et al. Science 08 Jan 2021: Vol. 371, Issue 6525, pp. 145-153). It was published by colleagues from the Immunology and Translational Oncology department of the University of Mainz and the two Biontech founders Özlem Türeci and Ugur Sahin are co-authors. So the scientists who developed the extremely efficient mRNA vaccine against COVID19. Surely this is also why the above work has received considerable media attention in the subsequent period, raising hopes among many MS patients.

Significance of Immune Tolerance

To understand what was done in the experiment, one must first delve deeper into immunology and explain an important fact: Adaptive immune cells (T and B lymphocytes) are not only capable of fighting and eliminating antigens. Under certain conditions, they can also tolerate antigens. Immune tolerance is even a very important and normal process. Because throughout our lives, immune cells must learn to behave tolerantly towards self-antigens (i.e. body’s own proteins) and aggressively combat foreign antigens (i.e. viruses, bacteria). A key feature of MS is the disturbed immunological tolerance to self-antigens of the central nervous system, leading to the formation of autoreactive T cells that attack the CNS.
Accordingly, there has long been a therapeutic approach to restore immune tolerance to CNS antigens in MS patients and thereby control or even cure the autoimmune disease MS. Unfortunately, despite promising approaches, no successes have been achieved so far – although the approach is logical in itself.

In the current Science paper on the “Multiple Sclerosis Vaccine”, a novel approach to tolerance induction is described. This is based on the mRNA system from Biontech, which is also the basis for the COVID19 vaccine. This vaccine relies on the fact that the blueprint of the SARS-CoV2 spike protein (i.e. the viral mRNA of the spike protein) is packaged in nanoparticles and injected. In the body, the nanoparticles merge with the membrane of antigen-presenting cells, which then produce the spike protein from the mRNA, present it on their surface, and thereby trigger an efficient immune response directed against the corona virus – and thus protect us against COVID19.

Vaccination against MS in Animal Model Experiment

In the “vaccination experiment against MS”, the same nanoparticle system was used as for COVID19. This time, the blueprint for proteins of the central nervous system (autoantigens) was packaged into the nanoparticles, not the blueprint of the viral spike protein. The authors were able to show that the selective delivery of autoantigens to antigen-presenting cells is possible and can thereby generate peripheral immune tolerance. Strictly speaking, the term “vaccination” is misleading, as it actually involves the opposite, namely tolerance induction.

The presentation of autoantigens in this non-inflammatory context led to a strong expansion of regulatory T cells, which are capable of inhibiting aggressive inflammation cells and suppressing tissue inflammation – as could be very impressively demonstrated in this work on the animal model of experimental autoimmune encephalomyelitis (EAE).

Results from animal model of MS not easily transferable to humans

And here lies the problem. The results refer to an animal model of MS and unfortunately it is a fact that strategies that work in mice with experimental autoimmune encephalomyelitis are not simply transferable to humans. In contrast to the animal model, the target antigens in MS are not known. This has led to antigen-specific therapeutic approaches that have worked under laboratory conditions, but in human experiments have sometimes unexpectedly led to an intensification of inflammation in the brain. So far, no antigen-specific therapeutic approach in multiple sclerosis has been successful.

The project of a “Multiple Sclerosis Vaccine” is a fascinating goal and any effort is to be welcomed – and the approach chosen here is a great demonstration of the possibilities of the new mRNA technology – but ultimately we still lack the basic understanding of the inflammatory processes to successfully use this technology in humans.
Therefore, I had to clearly advise my patient to take note of these basic scientific approaches with interest, but to decide in reality for a therapy that is now available and approved. Because experience shows that it takes up to 15 years from animal experimentation to the finished drug – and most potential approaches are not further developed.

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