New mRNA vaccine technology is causing waves today, as injections of COVID-19 based on it provide unparalleled effectiveness on other platforms. One of the successful photos, Comirnaty (BNT162b2), was developed with BioNTech technology and is being launched in the USA and the EU.
Now, BioNTech’s CEO, Ugur Sahin, MD, Ph.D., has led new research showing that an mRNA vaccine may also work in multiple sclerosis (MS).
In several mouse models of MS, Sahin’s team showed that an mRNA vaccine that encodes a disease-related autoantigen successfully improved the symptoms of MS in sick animals and prevented disease progression in rodents showing early signs of MS. The results were published in Science.
MS occurs when the immune system mistakenly attacks the protective myelin sheath that covers nerve cells in the brain and spinal cord. Existing treatments work by systematically suppressing the immune system. This can control MS, but it also leaves patients vulnerable to infections.
Sahin, along with colleagues at BioNTech and scientists at Johannes Gutenberg University in Mainz, hypothesized that an mRNA vaccine could work in a targeted way to help the immune system tolerate specific MS-related proteins without compromising normal immune function.
The team came up with an mRNA candidate that involved encoding genetic information for autoantigens that cause MS into fatty substances. A similar lipid nanoparticle is used in Comirnaty to protect the COVID-19 mRNA material until it reaches the target cells, where it produces the antigen protein.
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In mice with autoimmune encephalomyelitis, a model for human multiple sclerosis, the team found that the vaccine was processed by lymphoid antigen-presenting cells without triggering a systemic inflammatory immune response, even when administered at very high concentrations of antigen. It did not impair the animals’ ability to launch a protective immune response.
The vaccine blocked all clinical signs of multiple sclerosis in rats, while the control animals showed symptoms typical of the disease. In mice that started with the mRNA vaccine when small signs of illness, such as tail paralysis, were observed, the treatment prevented the disease from progressing and restored motor functions, the team reported.
In treated mice, the researchers observed lower levels of CD4 + T cells specific for antigens and infiltrants in the brain and spinal cord, and T cells in the spleen showed low expression of certain markers that are critical for immune cells to be able to enter the central nervous system.
Furthermore, the treatment led to the expansion of regulatory T cells, or Treg cells. This is important because MS is a complex disease in which specific autoantigens may differ from one patient to another. But Treg cells offer a more general “spectator tolerance”, which suppresses T cells against other antigens in inflamed tissue, the researchers explained in the article.
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MRNA technology is being hailed as a revolution in the vaccine space. Comirnaty, Pfizer partner at BioNTech, demonstrated 95% effectiveness in preventing COVID-19 in its phase 3 test, leading an industry observer to predict that success will “open the floodgates” of mRNA application, especially in infectious diseases .
Sahin originally founded BioNTech to translate the idea of mRNA into immunotherapy against cancer, but the company accepted the challenge of COVID-19 in the midst of the pandemic. Now, Sahin and his colleagues believe that their research shows that mRNA vaccines are also promising in the treatment of MS.
As COVID-19 has shown, mRNA vaccines can be designed quickly and mRNA can encode virtually any autoantigen. “Thus, adapting treatment for the disease-causing antigens of individual patients is conceivable, similar to what has been successfully performed in the context of personalized cancer vaccines,” wrote the researchers in the study. The combination of mRNAs may allow control of even more complex autoimmune diseases, they suggested.