Autoimmune diseases such as multiple sclerosisthe Diabetes type 1o la rheumatoid arthritis They could be completely reversed without impeding the activity of the rest of the immune system thanks to a new type of vaccine –’reverse vaccine’– developed by scientists at the Pritzker School of Molecular Engineering (PME) at the University of Chicago.
Traditional vaccines work by teaching our immune system to identify a virus or bacteria as an enemy to fight. However, the ‘reverse vaccine’ acts in the opposite way and what it does is remove a molecule from the immune system’s memory. Erasing the immune memory would be harmful in the case of infectious diseases because if our defenses remember a harmful pathogen it is easier to eliminate it, but it can stop autoimmune reactions such as those that occur in multiple sclerosis and other pathologies in which the immune system attacks the patient’s healthy tissues.
Reverse vaccination takes advantage of how the liver naturally marks the molecules of broken down cells with “do not attack” flags to prevent autoimmune reactions to cells that die by natural processes. The PME researchers coupled an antigen (a molecule attacked by the immune system) with a molecule that resembles a fragment of an aging cell that the liver would recognize as a friend, rather than a foe. The team demonstrated how the vaccine could successfully stop the autoimmune reaction associated with a multiple sclerosis-like disease.
The reverse vaccine caused the immune system to stop attacking myelin, allowing the nerves to function again and reversing the symptoms of multiple sclerosis in the animals
“In the past, we showed that we could use this approach to prevent autoimmunity,” he said. Jeffrey Hubbell, Eugene Bell Professor of Tissue Engineering and senior author of the new paper. “But what’s interesting 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 the real-world context.” The findings have been published in Nature Biomedical Engineering.
Control the immune response to avoid autoimmune diseases
Hubbell and his colleagues knew that the body has a mechanism to ensure that immune reactions are not triggered in response to each damaged cell, a phenomenon known as peripheral immune tolerance, which takes place in the liver. They recently discovered that tagging molecules with a sugar known as N-acetylgalactosamine (pGal) could mimic this process, sending the molecules to the liver, where tolerance to them develops.
“The idea is that we can attach any molecule we want to pGal and this gives it “It will teach the immune system to tolerate it.”Hubbell explained. “Instead of accelerating immunity as with a vaccine, we can reduce it in a very specific way with a reverse vaccine.”
The researchers focused on a disease similar to multiple sclerosis in which the immune system attacks myelin, causing weakness and numbness, loss of vision and, eventually, mobility problems and paralysis. They linked myelin proteins to pGal and tested what effect the new reverse vaccine had. They found that the immune system stopped attacking myelin, allowing nerves to function properly again and reversing disease symptoms in the animals.
They performed other experiments in which they showed that the same approach worked to minimize other ongoing immune reactions. These scientists acknowledge that more research is needed to study Hubbell’s pGal compounds in humans, but initial Phase I safety trials have already been conducted in people with celiac disease and Phase I safety trials are underway in multiple sclerosis. “There are no clinically approved reverse vaccines yet, but we are incredibly excited about the advancement of this technology,” concludes Hubbell.