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A groundbreaking form of vaccine that avoids suppressing the immune system has exhibited promising results in the laboratory, showing potential to completely reverse autoimmune conditions such as arthritis, multiple sclerosis, Type-1 diabetes, and Crohn’s disease.
Typically, a vaccine educates the human immune system to identify a virus or bacteria as a threat to be countered. Presently, autoimmune diseases are generally managed with drugs that broadly suppress the immune response.
The innovative “inverse vaccine,” developed by researchers at the University of Chicago, takes the opposite approach: it erases the immune system’s memory of a specific molecule.
Although this immune memory wipeout would be undesirable for infectious diseases, it can halt autoimmune responses seen in conditions like multiple sclerosis, Type-1 diabetes, rheumatoid arthritis, or Crohn’s disease, where the immune system erroneously attacks healthy tissues.
Described in the journal Nature Biomedical Engineering, the inverse vaccine leverages the liver’s natural labeling of molecules from decomposed cells with “do not attack” signals to prevent autoimmune reactions to naturally occurring cell death.
“We previously demonstrated this approach to prevent autoimmunity,” stated lead author Jeffrey Hubbell, Professor in Tissue Engineering at the university’s Pritzker School of Molecular Engineering (PME). “What is particularly exciting about this work is that we’ve shown its effectiveness in treating ongoing inflammation in diseases like multiple sclerosis, which is more applicable in a real-world context,” he added.
The human body has a mechanism to ensure that immune responses don’t occur in reaction to every damaged cell—an occurrence known as peripheral immune tolerance, orchestrated in the liver. The team recently discovered that tagging molecules with a sugar called N-acetylgalactosamine (pGal) could emulate this process, directing the molecules to the liver where tolerance towards them develops.
“The concept is that we can attach any molecule to pGal, and it will teach the immune system to tolerate it,” explained Hubbell. “Rather than stimulating immunity as with a vaccine, we can specifically suppress it with an inverse vaccine.”
In this recent study, the researchers targeted a disease resembling multiple sclerosis, where the immune system attacks myelin, resulting in weakness, numbness, vision loss, and eventually, mobility issues and paralysis.
By linking myelin proteins to pGal and testing the new inverse vaccine’s effects, they found that the immune system ceased its assault on myelin, enabling nerves to function properly once more and reversing disease symptoms in animals.
In a series of additional experiments, the scientists demonstrated that the same approach effectively reduced other ongoing immune responses.
“While these treatments can be highly effective, they also suppress the necessary immune responses to combat infections, resulting in numerous side effects,” noted Hubbell. “If we could administer an inverse vaccine to patients instead, it could be much more targeted and lead to fewer side effects.”
