The most important thing to remember is that a typical vaccine trains the body's immune system to recognize foreign invaders, such as viruses and bacteria, as enemies and then attack them.
This clearing of immune memory is obviously undesirable for infectious diseases but could stop autoimmune responses such as those seen in multiple sclerosis, type 1 diabetes, rheumatoid arthritis, and Crohn's disease, in which the immune system attacks the body's healthy tissues.
The study was published on September 7, 2023, in Nature Biomedical Engineering, describing a novel "reverse vaccine" strategy that combines N-acetylgalactosamine (pGal) with antigens. This pGal-antigen treatment induced antigen-specific tolerance in a mouse model of experimental autoimmune encephalomyelitis and inhibition of antigen-specific responses to a DNA-based apicobacterial vaccine in non-human primates. inhibition of antigen-specific responses.
This study demonstrates that this pGal-antigen-based "reverse vaccine" strategy, which addresses antigen-specific inflammatory T-cell responses by invoking immune tolerance mechanisms, can be applied to a wide range of autoimmune diseases, bringing a novel therapeutic approach to autoimmune disorders such as multiple sclerosis, type 1 diabetes mellitus, and Crohn's disease without having to shut down the immune system.
T-cells in the immune system are responsible for recognizing cells and molecules we don't want, from viruses and bacteria to cancer cells, then treating them as foreign and removing them. Once T cells launch their initial attack on antigens, they retain a memory of these invaders so that they can be removed more quickly the next time they invade.
However, T cells sometimes make mistakes and recognize healthy cells as foreign. For example, T cells in patients with Crohn's disease mistakenly attack small intestinal cells, while T cells in patients with multiple sclerosis mistakenly attack the protective layer of myelin surrounding nerve cells.
There is a mechanism in the body that ensures that the immune response does not react to every damaged cell in the body, a phenomenon known as peripheral immune tolerance, which takes place in the liver. In recent years, the team has found that a molecule called N-acetylgalactosamine (pGal) mimics this process, and delivering the molecule to the liver creates tolerance for them.
The team believes that attaching chains of other molecules to pGal could teach the immune system to tolerate it, thus creating a "reverse vaccine" that suppresses immunity rather than activating it as a typical vaccine would.
In this latest study, the team focused on multiple sclerosis-like diseases, in which weakness and numbness, loss of vision, and ultimately loss of motor skills and paralysis result from an immune system attack that attacks the protective layer of myelin that surrounds nerve cells. The research team combined myelin with pGal and tested the effects of this "reverse vaccine". They found that in response to the vaccine, the immune system stopped attacking myelin, allowing the nerves to function properly again and reversing the symptoms of the disease in the animal model. In a series of other experiments, the team showed that the same approach could minimize other ongoing immune responses.
At this stage, treatments for autoimmune diseases usually involve drugs that broadly shut down the immune system. These treatments can be very effective, but they also block the immune response necessary to fight infections and have many side effects. If this "reverse vaccine" is used to treat autoimmune diseases, it will be more targeted and have fewer side effects.
Based on this research, two phase 1 clinical trials have been initiated, one for patients with celiac disease, a chronic, multi-organ autoimmune disease that involves the small intestine and is usually caused by gluten consumption, with chronic diarrhea, weight loss, edema, iron-deficiency anemia, and abdominal bloating. The other is for multiple sclerosis.