Author: Christine Chen
Editors: Ian Cho and Justin Tai
Artist: Helen Gong
The typical vaccine helps one’s immune system remember and erase unwanted infectious diseases. It is used to bolster the immune system, which is why we are required to get it. However, when it comes to autoimmune disorders, where the immune system attacks a person’s body, there has been a new vaccine that does almost the opposite: the inverse vaccine. As suggested by its name, it is used to stop autoimmune reactions, such as those in rheumatoid arthritis, multiple sclerosis, lupus, and more.
An example of the implementation of inverse vaccination is DNA inverse vaccines. They have been promising in targeting immune conditions like type 1 diabetes and multiple sclerosis. This approach keeps the rest of the immune system intact while still focusing on managing the autoimmune disease. Creating an inverse vaccine involves finding which part of the immune system is involved in autoimmune diseases and lessening these immune responses. In one study, special slides were developed containing potential autoantigens, substances that trigger the immune response. In the case of multiple sclerosis (MS), researchers have focused on myelin proteins, since MS is characterized by the immune system attacking the protective myelin sheath around the nerve fibers. Myelin is essential for nerve signal transmission, and in MS, the immune response attacks it, leading to demyelination, inflammation, and more. To understand the immune response better, researchers tested samples from blood and spinal fluid to reveal circulated antibodies that might lead to an insight into immune activity within the central nervous system. This whole process is used to identify the targets of autoimmune diseases. This is helpful because it directs the vaccine toward that target instead of subjecting the patient to vast amounts of immunosuppressants.
Creating these inverse vaccines usually involves nano molecules that contain cell material and are sent to the liver, since that is where T and B cells are. T cells primarily regulate the immune response and directly kill infected cells, while B cells produce antibodies that, when activated, can mark infected cells for destruction. They used a DNA vaccine for the first time to treat an autoimmune disease in 1996. It was used to focus on the part of the T-cell receptor that is involved in causing paralysis in animal models similar to MS. It changed the harmful type (Th1) to the protective type (Th2) for the T cells and stopped mice from paralysis.
Each autoimmune disease is different and will be treated with the vaccine differently. Plenty of research has gone into improving the vaccine’s effectiveness, by adjusting certain plasmids and promoting better expression to ensure that they are produced inside the cell to aid the cells in not marking beneficial cells as harmful. The first human trial for the inverse vaccine, BHT-3009, involved patients with multiple sclerosis. The vaccine targeted only one myelin protein at first because it was easier to regulate the effects of the vaccine. These were performed safely, followed by positive trends in MRI scans, and reduced the immune cells that react to myelin. In the second trial, patients who received BHT-3009 also showed a decrease in new lesions and antibody levels against myelin components compared to those receiving nothing. It has also been shown to work well even after damage to myelin.
Despite all this progress, reverse vaccines still haven’t unlocked their full potential. There is more to understand about the mechanisms that produce tolerance, and the mechanisms of how the current reverse vaccines work are still in question. Still, this is a hopeful first step in developing a solution to autoimmune diseases without subjecting patients to immunosuppressants that risk them having other complications.
Citations:
L;, Steinman. “Inverse Vaccination, the Opposite of Jenner’s Concept, for Therapy of
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Williams, Sarah C.P. “‘inverse Vaccine’ Shows Potential to Treat Multiple Sclerosis and
Other Autoimmune Diseases.” Pritzker School of Molecular Engineering | The University of
Chicago, 11 Sept. 2023, pme.uchicago.edu/news/inverse-vaccine-shows-potential-treat-
Willyard, Cassandra. “How Inverse Vaccines Might Tackle Diseases like Multiple Sclerosis.”
MIT Technology Review, MIT Technology Review, 25 Sept. 2023,
“Inverse Vaccines: A New Hope for Millions of Patients with Autoimmune Diseases.”
Alcimed, www.alcimed.com/en/insights/inverse-vaccines/#:~:text=To%20design
Accessed 28 Sept. 2024.
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