BioNTech’s experimental non-inflammatory vaccine — designed to dampen the abnormal immune responses seen in multiple sclerosis (MS) against myelin — delayed the onset and lessened the severity of symptoms in a mouse model of MS, a study reports.
Importantly, treated mice showed no signs of overall immune suppression, suggesting that this type of therapy may overcome the downsides associated with current immunosuppressive therapies for MS.
These data support advancing this vaccine, and possibly bringing it into testing in patients.
The study, “A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis,” was published in the journal Science.
MS is an autoimmune disease in which the immune system mistakenly attacks myelin, the fatty protective sheath that covers nerve fibers. As such, the main goal in treatment development for MS and other autoimmune conditions is to specifically suppress the cells that drive these immune attacks, without promoting overall immune suppression.
However, this has proven challenging. Current MS disease-modifying therapies promote, in one way or another, a general suppression of the immune system or of its key players, potentially impairing immune responses against real threats and increasing the risk of infections.
According to BioNTech, its experimental, non-inflammatory vaccine may revolutionize MS treatment by re-educating regulatory T-cells (Tregs) — a type of immune cell that typically dampens immune and inflammatory responses — to tolerate myelin-associated proteins and suppress immune reactions against them.
Notably, this vaccine differs from conventional vaccines in two main aspects. First, instead of stimulating a person’s immune system to recognize, memorize, and readily fight specific microbes or molecules, it promotes immune tolerance to a particular molecule.
Secondly, it does so by delivering messenger RNA (mRNA) — the intermediate molecule generated from DNA that serves as a template for protein production — rather than protein fragments to cells. This means that after entering cells, the mRNA containing the instructions to produce a specific protein is used by the cell to produce that protein, which then is “shown” to immune cells.
In the specific case of MS, the vaccine’s mRNA was designed to contain the instructions to produce a myelin-specific protein mistakenly targeted by immune cells in MS, and modified so as to be less likely to promote immune responses.
The therapy uses tiny particles to deliver the mRNA to dendritic cells, a type of immune cell that presents molecules to other immune cells, including Tregs, promoting immune tolerance when in a non-inflammatory context — the situation intended with this vaccine.
Researchers at BioNTech, along with colleagues at research organizations and institutes of the Johannes Gutenberg University Mainz, in Germany, tested the effects of the mRNA vaccine in several mouse models of MS based on the experimental autoimmune encephalomyelitis (EAE) model.
Results from all evaluated mouse models showed that the vaccine prevented disease development or, in mice with early stage disease, halted its progression and restored the animals’ motor function.
Treated mice also showed considerably few pro-inflammatory immune cells in the brain and spinal cord, as well as lesser myelin damage.
Further analyses showed that these benefits were associated with an expansion of a specific population of Tregs suppressing immune cells and responses against the myelin-specific molecule encoded by the mRNA vaccine.
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