https://pme.uchicago.edu/news/inverse-vaccine-shows-potential-treat-multiple-sclerosis-and-other-autoimmune-diseases
https://archive.ph/fpJOr
“Inverse vaccine” shows potential to treat multiple sclerosis and other autoimmune diseases
A new type of vaccine developed by researchers at the University of Chicago’s Pritzker School of Molecular Engineering (PME) has shown in the lab setting that it can completely reverse autoimmune diseases like multiple sclerosis and type 1 diabetes— all without shutting down the rest of the immune system.
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 like those seen in multiple sclerosis, type I diabetes, or rheumatoid arthritis, in which the immune system attacks a person’s healthy tissues.
The inverse vaccine, described in Nature Biomedical Engineering, 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. PME researchers coupled an antigen — a molecule being attacked by the immune system— with a molecule resembling a fragment of an aged cell that the liver would recognize as friend, rather than foe. The team showed how the vaccine could successfully stop the autoimmune reaction associated with a multiple-sclerosis-like disease.
“In the past, we showed that we could use this approach to prevent autoimmunity,” said Jeffrey Hubbell, the Eugene Bell Professor in Tissue Engineering and lead author of the new paper. “But what is so exciting about this work is that we have shown that we can treat diseases like multiple sclerosis after there is already ongoing inflammation, which is more useful in a real-world context.”
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In the new study, the researchers focused on a multiple-sclerosis-like disease in which the immune system attacks myelin, leading to weakness and numbness, loss of vision and, eventually mobility problems and paralysis. The team linked myelin proteins to pGal and tested the effect of the new inverse vaccine.The immune system, they found, stopped attacking myelin, allowing nerves to function correctly again and reversing symptoms of disease in animals.
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https://www.nature.com/articles/s41551-023-01086-2
https://archive.ph/1rJ4c
Synthetically glycosylated antigens for the antigen-specific suppression of established immune responses
Abstract
Inducing antigen-specific tolerance during an established immune response typically requires non-specific immunosuppressive signalling molecules. Hence, standard treatments for autoimmunity trigger global immunosuppression. Here we show that established antigen-specific responses in effector T cells and memory T cells can be suppressed by a polymer glycosylated with N-acetylgalactosamine (pGal) and conjugated to the antigen via a self-immolative linker that allows for the dissociation of the antigen on endocytosis and its presentation in the immunoregulatory environment. We show that pGal–antigen therapy induces antigen-specific tolerance in a mouse model of experimental autoimmune encephalomyelitis (with programmed cell-death-1 and the co-inhibitory ligand CD276 driving the tolerogenic responses), as well as the suppression of antigen-specific responses to vaccination against a DNA-based simian immunodeficiency virus in non-human primates. Our findings show that pGal–antigen therapy invokes mechanisms of immune tolerance to resolve antigen-specific inflammatory T-cell responses and suggest that the therapy may be applicable across autoimmune diseases.