Turning the Tables on Autoimmune Diseases

‘Inverse vaccine’ has the potential to reverse symptoms while leaving immune systems intact

Our immune systems are wonderful things. When foreign pathogens enter our bodies, our immune systems gather an army of T cells and drive off the invaders, trying to rid our bodies of the illness. Even better, our immune systems remember that particular antigen, making our response faster and better the next time we encounter it. Most times, our immune systems work just fine. But not always.

About 10% of people have some sort of autoimmune disease, in which their immune systems mistake healthy tissue for unwelcome intruders and attack it. Doctors have identified more than 80 types of autoimmune disease, and they attack a whole host of body parts. In the case of multiple sclerosis, the immune system attacks myelin, fatty tissue that coats nerve fibers. In type 1 diabetes, the immune system attacks islet cells in the pancreas that are responsible for producing insulin.

What’s common to all autoimmune diseases is that we don’t have a cure. But University of Chicago researchers might have discovered a treatment that can reverse the effect of autoimmune diseases and stop symptoms without inhibiting the rest of the immune system. The “inverse vaccine,” developed by the scientists at the Pritzker School of Molecular Engineering, teaches the immune system to forget normal cells, a flip on the way regular vaccines teach the immune system to recognize and remember foreign cells. They published their findings in Nature Biomedical Engineering.

“Rather than rev up immunity as with a vaccine, we can tamp it down in a very specific way with an inverse vaccine,” lead author Prof. Jeff Hubbell said.

Teaching Tolerance

In developing the inverse vaccine, they wanted to mimic the body’s natural peripheral immune tolerance, in which the liver flags molecules from cells that die naturally to prevent the immune system from attacking them. The sugar N-acetylgalactosamine, also known as pGal, can have the same effect.

“The idea is that we can attach any molecule we want to pGal and it will teach the immune system to tolerate it,” Hubbell said.

Those molecules go to the liver, where the cells responsible for peripheral immune tolerance recognize them and instruct T cells to protect them rather than attack them.

The researchers successfully tested their inverse vaccine in mice with autoimmune encephalomyelitis, a condition similar to MS. The treatment reversed the symptoms, preventing the mice’s immune systems from attacking the myelin coating nerves in their brains and spinal cords. The inverse vaccine then worked on other immune reactions, indicating that it could treat a whole host of autoimmune diseases.

That would be welcome news to those with MS and other autoimmune conditions. Current drug treatments tend to shut down the entire immune system, leaving patients vulnerable to infection.

With animal trials successful the inverse vaccine moved to Phase I safety trials on MS patients, and a Phase I safety trial has begun on celiac patients using a therapy based on the team’s preclinical work. Anokion SA is conducting the trials.

“In the past, we showed that we could use this approach to prevent autoimmunity,” Hubbell said. “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.”

Whereas autoimmune drug treatments wear off after a while and have to be given repeatedly, Hubbell hopes this treatment will prove long-lasting, even potentially curative. As yet, there are no inverse vaccines clinically approved, but the researchers are excited about the prospects of theirs.

Our immune systems are capable of amazing things. Sometimes they need a little help. There are more phases of clinical trials to go before this treatment reaches approval, but if it does, it could do a lot of bodies a lot of good.