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'Inverse' vaccines may hold key to challenge autoimmune diseases

Reverse or inverse vaccines work by targeting only the specific part of the immune system that's behind diseases such as lupus, multiple sclerosis, psoriasis, rheumatoid arthritis and Type 1 diabetes, experts say.

By Brian P. Dunleavy, UPI

Published Jun 30, 2025 11:35 AM EDT | Updated Jun 30, 2025 11:49 AM EDT

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Reverse or inverse vaccines work differently from conventional immunizations like the flu shot and currently available immunosuppressant treatments for autoimmune conditions. (Photo credit: RF_Studio/Pexels)

NEW YORK, June 30 (UPI) -- For the millions of Americans battling autoimmune disorders, new hope may be on the horizon in the form of reverse or inverse vaccines -- injections that target a specific part of the immune system, experts told UPI.

However, these injections work differently from conventional immunizations like the flu shot and currently available immunosuppressant treatments for autoimmune conditions.

They work by targeting only the specific part of the immune system that's behind diseases such as lupus, multiple sclerosis, psoriasis, rheumatoid arthritis and Type 1 diabetes, the experts say.

"Inverse vaccines are being developed to treat undesired immune responses, [and] for these situations, the body is reacting to something that is not dangerous," said Lonnie Shea, a researcher in biomedical engineering at the University of Michigan who has studied inverse vaccines and worked on some of the key technology behind them.

"A vaccine activates an immune response to a specific antigen," Shea told UPI via email. Inverse vaccines are being developed to treat undesired immune responses, [and] for these situations, the body is reacting to something that is not dangerous.

Essentially, an inverse vaccine "aims to decrease the response to a specific antigen, like insulin in Type 1 diabetes," he added.

First line of defense

When healthy, the immune system is the body's first line of defense against diseases such as cancer and infections caused by viruses and bacteria, according to the National Institutes of Health.

However, if the immune system isn't working properly, it can erroneously attack healthy cells, tissues and organs, causing autoimmune diseases that can affect any part of the body, weakening function and potentially leading to death, the NIH says.

More than 80 autoimmune diseases are known, some of which are caused by exposure to environmental toxins and have no discovered cure. At least 15 million people in the United States, or about 5% of the population, have an autoimmune disease, the agency reports.

Although no cure exists for these conditions, symptoms can be managed with drugs called immunosuppressants, which as the name suggests "broadly reduces your immune system response," Shea said.

These drugs, which are typically administered via monthly injections, can have significant side effects, including making those taking them more susceptible to infections, according to the NIH.

Many people taking them also have to be careful taking traditional vaccines, such as flu shot or COVID-19 shots because of their impact on the immune system.

Training the immune system

Developed by researchers at the University of Chicago and elsewhere, inverse vaccines use synthetic nanoparticles attached to specific disease-related proteins, or antigens, to train certain parts of the immune system to behave differently, limiting the attacks that cause autoimmune diseases, neurologist Dr. Lawrence Steinman said.

With the inverse vaccines currently being studied, the nanoparticles are designed to mimic human cell death, which is a normal process in the human body, according to the 2021 study that first documented their effectiveness in people with celiac disease, another autoimmune disorder.

Dying cells are considered foreign bodies, but the human immune system knows not to attack them.

As a result, with the nanoparticles in inverse vaccines, the immune system can be trained not to attack them, or the proteins attached to them, which effectively short-circuits the process behind autoimmune diseases, Steinman said.

"Instead of immunizing the recipient to a viral infection, the inverse vaccine tolerizes the immune system, so it will not attack our own tissues," Steinman, who has written about inverse vaccines, told UPI in an email.

Several companies are running clinical trials of inverse vaccines, including Cour Pharma, which recently completed successful phase 2 clinical trials for their use in celiac disease and another autoimmune disease, primary biliary cholangitis, according to Shea at the University of Michigan, one of the researchers who started the company.

Additional trials -- phase 2 studies are the second stage in the drug research and development process -- are starting for myasthenia gravis and Type 1 diabetes, he added.

Although more research is needed before the shots become available, a process that could take five years or more, inverse vaccines offer key advantages, Shea said.

For example, unlike immunosuppressants with their monthly dosing, the effects of inverse vaccines appear to last longer, perhaps for as much as a year, similar to conventional vaccines, research suggests.

They may also work for people with severe, life-threatening allergies, such as peanut allergies, according to Shea, who has published a study in this area using mice.

However, there's also the "risk that instead of tolerizing the human immune system to the target, the process induces conventional immunization, which would make autoimmune conditions like Type 1 diabetes and multiple sclerosis worse," Steinman said.

However, "We have come close to success in some early-stage trials," he said "Thus far, none of the results are sufficiently robust for submission in the FDA approval process."

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