The new mRNA for vaccine technology is making headlines these days because COVID-19 shots deliver efficiencies that are unmatched by other platforms. One of the most successful recordings, Comirnaty (BNT162b2), was developed using BioNTech’s technology and is being rolled out in the US and EU.
Now, BioNTech CEO Ugur Sahin, MD, Ph.D., has led new research showing that an mRNA vaccine can also work in multiple sclerosis (MS).
In several mouse models of MS, Sahin’s team showed that an mRNA vaccine encoding a disease-related motor antigen successfully improved MS symptoms in sick animals and prevented the progression of diseases 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. It can control MS, but it also leaves patients vulnerable to infections.
Sahin, along with colleagues from BioNTech and scientists at the Johannes Gutenberg University of Mainz, hypothesized that an mRNA vaccine could work in a targeted way to help the immune system tolerate specific MS-related proteins without compromising the to impair normal immune function.
The team came up with an mRNA candidate who wrapped the genetic information encoding MS-causing self-antigens in 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 antigenic protein.
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In mice with autoimmune encephalomyelitis, a model for human MS, the team found that the vaccine is processed by lymphoid antigen cells without eliciting a systemic inflammatory immune response, even when delivered at very high antigen concentrations. It did not impair the animals’ ability to initiate a protective immune response.
The vaccine blocked all clinical signs of MS in mice, while control animals experienced the typical symptoms of the disease. In mice that started the mRNA vaccine when small signs of disease such as paralysis of the tail were noticed, the treatment prevented further progression of the disease and restored motor functions, the team reported.
In treated mice, the researchers observed lower levels of infiltrating and antigen-specific CD4 + T cells in the brain and spinal cord, and the T cells in the spleen showed a low expression of certain markers that are critical for the immune cells to to enter the central nervous system.
What’s more, the treatment has led to the expansion of regulatory T cells, or Treg cells. This is important because MS is a complex disease in which the specific self-antigens may differ from patient to patient. But Treg cells provide a more common “bypass tolerance,” which suppresses T cells against other antigens in the inflamed tissue, the researchers explained in the article.
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The mRNA technology is considered a revolution in vaccine space. BioNTech’s Pfizer partner Comirnaty has shown 95% efficiency in preventing COVID-19 in its Phase 3 trial, leading to one viewer in the industry predicting that success will open the floodgates of mRNA administration, especially in contagious diseases.
Sahin originally founded BioNTech to translate the mRNA idea into cancer immunotherapy, but the firm tackled the challenge of COVID-19 amid the pandemic. Now, Sahin and colleagues believe that their research shows that mRNA vaccines are also promising to treat MS.
As shown by COVID-19, mRNA vaccines can be rapidly engineered and can encode mRNA for virtually any motor antigen. “Adjusting the treatment for the disease-causing antigens of individual patients is therefore conceivable, similar to those that have been successfully performed in the design of personalized cancer vaccines,” the researchers wrote in the study. The combination of mRNAs could enable control of even more complex autoimmune diseases, they suggested.