A vaccine developed by researchers at the University of Chicago’s Pritzker School of Molecular Engineering (PME) has demonstrated in the lab that it can reverse autoimmune diseases without compromising the rest of the immune system. In a study in Nature Biomedical Engineering, the team show that the “inverse vaccine” works by removing the immune system’s memory of a specific molecule. While this would be less than ideal for infectious diseases, in autoimmune reactions where the immune system attacks healthy tissues, it could be a significant step forward.
How does it work?
The team knew that the body has a mechanism to prevent immune reactions to every damaged cell. This is a phenomenon known as peripheral immune tolerance and is carried out by the liver. The vaccine exploits the liver’s role of marking molecules from broken-down cells with “do not attack” signals to prevent autoimmune reactions to cells that die by natural processes. Recently, they found that tagging molecules with a sugar known as N-acetylgalactosamine (pGal) could mimic the process, sending molecules to the liver where a tolerance can be developed.
Previously, suggests Professor Jeffrey Hubbell, this approach has been used to prevent autoimmunity.
“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.”
This real-world context could have applications for Chron’s disease, where the immune system attacks cells of the small intestine, or multiple sclerosis, where T cells attack myelin, the protective coating around nerves. Professor Hubbell explains that by attaching “any molecule we want” to pGal, they can teach the immune system to “tolerate it”.
“Rather than rev up immunity with a vaccine, we can tamp it down in a very specific way with an inverse vaccine.”
Spotlight on disease
In the recent study, the team focused on a multiple-sclerosis-like disease, in which the immune system attacks myelin. This causes weakness and numbness, loss of vision, and eventually leads to mobility problems or paralysis. The myelin proteins were linked to pGal, which encouraged the immune system to stop attacking them. Thus, nerves could function at potential again and the symptoms of disease were reversed in animals.
In other experiments, the researchers showed that the same approach was effective in minimising other ongoing immune reactions. So, what are the next steps? Although current treatment options are “very effective”, they have “a lot of side effects”, says Professor Hubbell.
“If we could treat patients with an inverse vaccine instead, it could be much more specific and lead to fewer side effects.”
Further research is needed to understand the effects in humans, but initial Phase I safety trials have been carried out in people with coeliac disease. Phase I safety trials are underway in multiple sclerosis.
“There are no clinically approved inverse vaccines yet, but we’re incredibly excited about moving this technology forward.”
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