Researchers at the University of Chicago's Pritzker School of Molecular Engineering (PME) have introduced an innovative concept known as the "inverse vaccine," which shows promising potential in treating autoimmune diseases, including multiple sclerosis and type 1 diabetes. This groundbreaking approach aims to reverse autoimmune conditions without compromising the entire immune system.
Traditional vaccines are designed to teach the immune system to recognize and attack specific viruses or bacteria. In contrast, the inverse vaccine takes a different approach by erasing the immune system's memory of a particular molecule. While this immune memory suppression is not suitable for infectious diseases, it holds great promise for halting autoimmune responses, such as those seen in multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, where the immune system mistakenly attacks healthy tissues.
Published in the journal Nature Biomedical Engineering, the inverse vaccine leverages the liver's natural ability to tag molecules from naturally decaying cells with "do not attack" signals, thereby preventing autoimmune reactions to cells undergoing natural processes. PME researchers achieved this by combining an antigen, a molecule targeted by the immune system, with another molecule resembling a fragment of aged cells that the liver recognizes as friendly rather than hostile. The vaccine's effectiveness was demonstrated in halting the autoimmune reaction associated with a disease resembling multiple sclerosis.
Jeffrey Hubbell, the Eugene Bell Professor in Tissue Engineering and the lead author of the study, highlighted the significance of their findings, stating, "In the past, we showed that we could use this approach to prevent autoimmunity. 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."
The immune system's T cells play a pivotal role in identifying and eliminating foreign cells and molecules, including viruses, bacteria, and cancerous cells. However, T cells can make errors by mistakenly identifying healthy cells as foreign invaders, leading to autoimmune diseases such as multiple sclerosis, where T cells attack the protective myelin coating around nerves.
Recognizing the liver's role in peripheral immune tolerance, which prevents immune responses against every damaged cell in the body, the researchers developed a technique involving tagging molecules with N-acetylgalactosamine (pGal). This mimics the liver's process, directing the molecules to the liver, where immune tolerance develops. Unlike traditional vaccines that boost immunity, the inverse vaccine takes a highly specific approach, dampening immune responses.
In their study, the researchers addressed a multiple-sclerosis-like disease in which the immune system attacks myelin, leading to symptoms such as weakness, numbness, vision loss, and mobility issues. By linking myelin proteins to pGal and administering the inverse vaccine, the researchers observed that the immune system ceased its assault on myelin, allowing nerves to function normally and reversing disease symptoms in animal subjects. The approach also showed promise in mitigating other ongoing immune reactions.
Autoimmune diseases are currently treated with broad-spectrum immunosuppressive drugs. While effective, these treatments have significant side effects due to their non-specific nature. The "inverse vaccine" offers the potential for highly targeted treatments, reducing side effects and enhancing patient outcomes.
Initial phase I safety trials for a glycosylation-modified antigen therapy based on this research have already been conducted in individuals with celiac disease, with ongoing trials for multiple sclerosis. These trials are being carried out by the pharmaceutical company Anokion SA, which played a crucial role in funding the research. The Alper Family Foundation also contributed to the project.
While clinically approved inverse vaccines are not yet available, the researchers are enthusiastic about advancing this groundbreaking technology and its potential to revolutionize autoimmune disease treatment.