Researchers have developed a "reverse vaccine" that reverses the damage caused by the immune system mistakenly attacking healthy organs and tissues in autoimmune diseases such as multiple sclerosis, type 1 diabetes and rheumatoid arthritis. It could pave the way to treating these diseases without suppressing the entire immune system.
Typically, vaccines teach the body's immune system to recognize viral or bacterial invaders as enemies that need to be destroyed. Now, researchers at the University of Chicago have created a "reverse vaccine" that does exactly the opposite.
The new vaccine erases the immune system's memory of a molecule, which is undesirable when fighting pathogens but may prove to be a treatment in autoimmune diseases.
The job of immune system T cells is to recognize specific foreign antigens on the surface of harmful cells and attack them. However, T cells sometimes make mistakes. In autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes and rheumatoid arthritis, T cells react on their own, mistaking healthy organs and tissues for foreign organisms.
Researchers are aware of the importance of the liver in mediating local and systemic tolerance to self- and foreign antigens. They exploit the liver's natural mechanism of breaking down molecules in cells with "do not attack" tags to prevent an autoimmune response to cells that naturally die. By coupling the antigen to molecules that resemble old cell debris, the liver recognizes it as a friend rather than a foe.
"In the past, we've shown that this approach can be used to prevent autoimmunity," said Jeffrey Hubbell, the study's corresponding author. "But what's exciting about this work is that we've shown that we can treat diseases like multiple sclerosis when inflammation is already present, which is more useful in the real world."
The liver's role in "peripheral immune tolerance" is a mechanism by which self-reactive T cells are deleted or become hypersensitive (nonfunctionally responsive to antigens), preventing the body from mounting an inappropriate immune response. In previous studies, the researchers found that tagging a molecule with a sugar called N-acetylgalactosamine (pGal) could mimic this process, delivering the molecules to the liver and creating tolerance to the molecules in the liver.
"The idea is that we can attach any molecule to pGal so that the immune system becomes tolerant to it," Hubbell said. "Instead of boosting immunity like you would with a vaccine, we suppress immunity in a very specific way with a reverse vaccine."
In the current study, the researchers focused on a mouse model of multiple sclerosis-like disease in which the immune system attacks myelin, the insulating sheath surrounding nerves. They linked the myelin protein to pGal and tested the effectiveness of the reverse vaccine, finding that the immune system stopped attacking myelin, allowing nerves to function normally and reversing disease symptoms.
Currently, autoimmune diseases are often treated with immunosuppressants that suppress the entire immune system, but this is not ideal.
"These treatments can be very effective, but they also block the immune response needed to fight off the infection, so they have a lot of side effects," Hubbell said. "If we could treat patients with a reverse vaccine, it would be more specific and have fewer side effects."
Phase 1 clinical trials are currently underway to assess the therapy's safety in people with multiple sclerosis. While there are currently no clinically approved reverse vaccines, researchers are incredibly excited about advancing this technology.
The research was published in the journal Nature Biomedical Engineering.