Personal care treatments

New technique to teach the immune system not to attack life-saving treatments

Biophysical characteristics of lipid nanoparticles for immunotherapy. (a) Surface exposure of different species of PS on the nanoparticles detected by the PSVue fluorescence signal. Changes in fluorescence I / I0 intensity were monitored as a function of total lipid concentration and fitted in GraphPad Prism using a single site total binding model with nonlinear least squares fit. Data are represented as mean ± SD. Two-way ANOVA followed by post-hoc Tukey analysis was performed to detect statistical significance, * P

Autoimmune diseases like type 1 diabetes, multiple sclerosis, and rheumatoid arthritis occur when an immune system mistakenly attacks proteins, cells, and organs in its own body. Not only do these conditions cause the body itself to attack, but they can also destroy the drugs used to treat them.

A reverse vaccination approach that my research team and I have developed, however, could cause the immune system to ignore autoproteins and prevent unwanted immune responses.

Autoimmunity destroys both the body and the treatment

Vital treatments for autoimmune diseases are complicated by the immune responses that work against them.

For example, people with Pompe disease are unable to produce the enzyme needed to break down complex sugars for energy. The buildup of these sugars in muscles and other organs impairs their ability to function and could be fatal. Although enzyme replacement therapy can help manage this condition, many people develop antibodies that direct their immune systems to destroy the treatment.

Once patients develop these unwanted antibodies, it becomes increasingly difficult to treat their conditions due to the limited availability of additional safe and effective therapies.

A reverse vaccination technique

Conventional vaccines generally train the immune system to recognize and attack specific parts of a pathogen that enter the body. The technique we propose reverses this concept and teaches the immune system to do the opposite: ignore and tolerate foreign proteins introduced into the body.

Autoimmune diseases occur when the immune system mistakenly sees a part of its own body as foreign and attacks it.

The vaccine that we have developed uses a particular lipid molecule, phosphatidylserine. PS is usually located in the inner layer of a cell’s surface membrane. When a cell dies from apoptosis, a natural process the body uses to shed damaged cells, the PS is exposed outside that cell. Upon exposure, PS sends out an “eat me” signal that recruits specialized cells to remove remaining debris from the now dead cell.

Our team had previously found that high levels of PS outside the cell also actively train the immune system to ignore exposed debris. So we wondered if PS could be used to help the immune system learn not to attack specific proteins.

We tested our concept in mice with hemophilia A. People with this genetic disease are unable to produce the blood clotting protein factor VIII. Although typical treatment involves administering factor VIII directly to patients to prevent uncontrollable bleeding, about a third develop an immune response against this protein after repeated exposure.

When we retrovaccinated the mice with factor VIII combined with an optimized form of PS, however, 75% of the mice did not develop an adverse immune response when they were then re-exposed to factor VIII over the four weeks. This meant that the immune system was able to learn that factor VIII was not harmful and remembered to tolerate it.

Next steps

Autoimmune diseases negatively affect the lives of millions of people in the United States and cost the health care system billions of dollars each year.

Our reverse vaccination technique could offer a potential way to prevent unwanted immune responses that render treatments ineffective or unusable. The next step is to translate the results of our lab study in mice into clinical trials in humans. We also want to use our reverse vaccination approach to treat other rare diseases and conditions for which treatment options are limited.

New treatment uses reverse vaccination to teach immune system not to attack life-saving drugs

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