“Inverse vaccine” shows potential to treat multiple sclerosis

September 18, 2023
A new type of vaccine developed by researchers has shown, in a lab setting, that it can reverse autoimmune diseases, such as multiple sclerosis, without shutting down the rest of the immune system.

The job of the immune system’s T cells is to recognize unwanted cells and molecules — ranging from viruses and bacteria to cancers — as foreign to the body and get rid of them. Once T cells launch an initial attack against an antigen, a molecule being attacked by the immune system, they retain a memory of the invader to eliminate it more quickly in the future. T cells can make mistakes, however, and recognize healthy cells as foreign. In people with MS, T cells mount an attack against myelin, the protective coating around nerves.

Researchers at the University of Chicago’s Pritzker School of Molecular Engineering knew the body has a mechanism for ensuring that immune reactions don’t occur in response to every damaged cell in the body — a phenomenon known as peripheral immune tolerance, which is carried out in the liver. They discovered in recent years that tagging molecules with a sugar known as N-acetylgalactosamine could mimic this process, sending the molecules to the liver where tolerance develops.

A typical vaccine teaches the human immune system to recognize a virus or bacteria as an enemy that should be attacked. The new “inverse vaccine” does just the opposite: it removes the immune system’s memory of one molecule. While such immune memory erasure would be unwanted for infectious diseases, it can stop autoimmune reactions such as those seen in MS.

In the study, researchers focused on experimental autoimmune encephalomyelitis, a mouse model of MS, in which the immune system attacks myelin, leading to weakness and numbness, loss of vision and, eventually mobility problems and paralysis. The inverse vaccine takes advantage of how the liver naturally marks molecules from broken-down cells with “do not attack” flags to prevent autoimmune reactions to cells that die by natural processes. Researchers coupled an antigen with a molecule resembling a fragment of an aged cell that the liver would recognize as friend, rather than foe. 

The team linked myelin proteins to N-acetylgalactosamine and tested the effect of the new inverse vaccine. The team showed how the vaccine could successfully stop the autoimmune reaction linked to EAE. The immune system, they found, stopped attacking myelin, allowing nerves to function correctly again and reversing symptoms of disease in animals. 

Results of animal model studies sometimes do not translate to humans and may be years away from providing a marketable treatment.

The findings were published in Nature Biomedical Engineering.

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