2023-09-29 05:00:00
How reverse vaccinations might stop autoimmune diseases
A new vaccination strategy is not intended to alert the immune system to germs, but rather to make it forget regarding supposed enemies. Such inverse vaccinations might stop and even reverse autoimmune diseases in which the body mistakenly attacks its own cells or cell structures. This is exactly what US researchers led by Jeffrey Hubbel and Scott Wilson from the University of Chicago managed to do in experiments with mice suffering from a disease similar to multiple sclerosis. They published their results in the specialist journal “Nature Biomedical Engineering”.
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Vaccinations normally teach the immune system which foreign molecules to attack. If it then detects bacteria or viruses, it takes action once morest the intruders. However, sometimes the immune system – or more precisely certain T cells – mistakenly attacks your own body. Then so-called autoimmune diseases arise: In type 1 diabetes, the immune system destroys the insulin-producing beta cells in the pancreas; in multiple sclerosis, it attacks the coating of nerve fibers. This myelin layer is important for the conduction of stimuli to the muscles. If it is destroyed, movement disorders and ultimately paralysis occur.
“Don’t attack”
Autoimmune diseases cannot yet be cured or stopped. At best you can slow down the process. This sometimes requires immunosuppressants, i.e. drugs that regulate the immune system on a broad front and therefore in a very non-specific manner. But this makes patients vulnerable to infections and cancer.
A few years ago, Hubbel’s group learned from the body how it prevents immune reactions once morest its own cell components. For example, if old cells are sorted out and broken down, their fragments – which no longer look like a normal cell – should not trigger the immune system. This is prevented by a kind of molecular label on the fragments that says: “do not attack”.
This label consists of a sugar residue with the short name pGal. During their training in the liver, defense cells of the innate immune system learn to tolerate molecules containing pGal. Healthy cells carry similar, slightly longer sugar labels. If the cells die at some point, an enzyme shortens this longer sugar to pGal. Basically, the body has to learn to reliably tolerate various substances that we often encounter: such as food, helpful bacteria in the intestines and pollen.
“So we thought, my goodness, if we do this [pGal] “If we can synthesize it and attach it to different antigens, then that should also ensure peripheral tolerance,” says Hubbel. In a previous experiment, the team prevented the development of type 1 diabetes in mice using the pGal label. Now they wanted to know whether an ongoing autoimmune disease might also be influenced.
Symptoms of the disease subsided
The team combined pGal with various myelin proteins and administered this inverse vaccine to experimental mice suffering from multiple sclerosis-like disease. The destruction of the myelin layer gradually leads to problems such as muscle weakness and deafness, loss of vision and ultimately to mobility problems and paralysis. However, following treatment with the inverse vaccine, the rodent’s immune system stopped attacking the myelin. The nerves were able to function properly once more and the symptoms of the disease subsided.
It is not yet clear whether this would also work in humans. Mouse treatment is still carried out quite early, five to seven days following the onset of the disease. It would therefore have to be tested whether the disease can be stopped and reversed even in a much more advanced stage.
In addition, multiple sclerosis is a complex disease in which the harmful immune reaction is not only directed once morest one antigen, said Lawrence Steinman from Stanford University to the US edition of Technology Review. Should you still rely on one main antigen or develop mixtures once morest several? The neuroimmunologist has been researching inverse vaccines for more than 15 years and is currently developing an inverse DNA vaccine once morest multiple sclerosis. This is not intended to make the immune system tolerant to myelin, but rather to downregulate its reaction to a molecule on the Epstein-Barr virus. The virus is considered a very likely trigger for the neurodegenerative disease.
Clinical studies started
Hubbel’s researchers hope that their inverse vaccine strategy might help not only once morest multiple sclerosis, but also once morest numerous autoimmune diseases. In fact, Hubbel co-founded the Swiss startup Anokion back in 2010, which is developing precisely such a vaccine. The candidate for relapsing-remitting multiple sclerosis is currently being investigated in a phase 1 safety study. A second vaccine once morest celiac disease, an autoimmune disease of the small intestine caused by gluten intolerance, is already in a phase 2 study that is also testing its effectiveness. It is said to help with gluten tolerance. The third candidate once morest type 1 diabetes is still in preclinical testing.
The idea of reverse vaccinations is not new. Researchers have been working on various ideas for decades, but so far without resounding success. Most recently, the German biotech company BioNTech and researchers from Mainz’s Johannes Gutenberg University reported in the journal “Science” in 2021 regarding promising mouse experiments with a messenger RNA (mRNA) vaccine once morest multiple sclerosis. “The vaccine delayed the onset of the disease and reduced the severity of the disease when the disease was already established.”the authors wrote.
Notably, immune tolerance was likely triggered via the lipid “packaging” around the mRNA vaccine. In the case of the Covid-19 vaccination, this packaging is designed to stimulate the immune system. However, with the multiple sclerosis vaccine it apparently had an immune-suppressing effect.
(jl)
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