Inverse vaccines are one of the hottest topics in medicine these days and with good reason. Approximately 1 in 10 people around the world have an autoimmune disease, and the number is rising. Unfortunately, the treatments that exist do not cure these diseases, and at best, may be termed blunt weapons because of the non-specific techniques that they employ. Treatments for autoimmune diseases, such as rheumatoid arthritis, type-1 diabetes, and multiple sclerosis typically involve the use of immune suppressants that suppress the entire immune system, exposing patients to a slew of unwanted side effects. In addition, when these drugs are withdrawn, patients frequently experience a relapse.
Autoimmune diseases are caused when the immune system attacks the body’s own tissues. Our immune systems are active in protecting us against infections and cancers by recognizing molecular patterns that are foreign to us. Normally, the immune system will attack these foreign molecules and destroy the cells carrying them, whether they be bacteria, viruses, fungi, or abnormal cells that have appeared in our bodies. And it does this without harming our own tissues. In autoimmune diseases, this system runs amok.
The immune system has two layers that protect us from the invasion of foreign germs. First, there is a layer of protection called the innate immune system, which is a non-specific system that reacts to any type of foreign molecule (antigens) entering the body. Second, there is the adaptive immune system that responds to specific intruders. Autoimmune diseases are caused when this system mistakenly identifies our own tissues as foreign and mounts an attack, destroying our tissues. In multiple sclerosis (MS), for example, the myelin sheaths of the nerves are attacked by the immune system.
Under normal circumstances, we are protected from attacks from the immune system, because the immune system is familiar with our own tissues and will not destroy them. During development, the cells of the immune system are “taught” which molecules in our bodies are our own. This separation of the various molecules into friend and foe is called tolerance, and there are several pathways in the body that lead to tolerance.
A cell that plays a central role in the establishment of tolerance is called the dendritic cell (DC), which presents molecules from invading germs to the immune system’s T and B-cells, giving them a chance to react if they recognize the molecule as foreign. Dendritic cells regulate the response of T-cells and control whether they mount an attack or differentiate into regulatory T-cells. Regulatory T-cells modulate the immune response and maintain tolerance.
Through special stimulatory molecules on the surface, dendritic cells can stimulate the immune system’s T-cells. If the stimulatory molecules are absent from the DC cell surface, activation of T-cells does not occur; rather, they develop tolerance for the particular molecule, or change into regulatory T-cells that modulate the immune response.
The immune response to foreign molecules may also be tempered by suppressive chemicals, such as IL10 or TGF-Beta. If dendritic cells present molecules (antigens) to the immune system, in the presence of suppressive chemicals, immune system cells do not react and instead learn that the molecule presented is a “friend,” thereby learning to tolerate it. Research is currently ongoing to create vaccines that attach foreign molecules (antigens) to nanoparticles that present the foreign molecules to immune system cells in the presence of suppressants. The suppressants prevent the differentiation of T-cells into T-cells that attack the particular molecule (effector T-cells). As a result, they differentiate into regulatory t-cells or develop a tolerance for the molecule.
Cells that are senescent go through a process called apoptosis or cell death, which destroys the cell, creating cellular debris. Cellular debris is recognized as our own and the immune system does not attack it. When cellular debris is attached to other specific molecules (antigens) and presented to T-cells in the liver and spleen, the attached molecules are also considered our own and our immune cells do not respond. They tolerate it. Alternatively, the T-cells differentiate into regulatory T-cells which temper the immune response.
Tolerance that develops in these cases is specific to the molecule that was presented to the T-cell. T-cells will therefore tolerate that specific molecule when they come into contact with it again. By hijacking these natural processes in the body, we can potentially cure autoimmune disease such as MS and type -1 diabetes, through forcing the immune system to once again develop tolerance for our own tissues.
Research is currently ongoing in the development of vaccines that will attach desired molecules (antigens) to nanoparticles, or liposomes, which will then present them to the immune system, just like dendritic cells do, in the absence of stimulatory molecules, in the presence of suppressants, or attached to cellular debris. This will force the immune system to once again recognize our tissues as our own. Conventional vaccines stimulate the immune system to attack a particular molecule or germ and rid the body of it. These vaccines do the exact opposite. They induce the immune system to “embrace and befriend” a particular molecule. Because of this, these vaccines are called “inverse vaccines.”
This approach is especially attractive, because it is targeted, and the rest of the immune response remains intact to protect us from other foreign molecule entering the body. Thus, the danger of infection and cancer seen during conventional treatments for autoimmune diseases, employing broad immune suppressants, is eliminated. Inverse vaccines might benefit transplant recipients as well, if they are vaccinated with the molecules from the cells in the transplant and tolerance is induced. This is one way rejection in organ transplant recipients might be overcome.
A cure for autoimmune diseases is on the horizon. It is just a matter of time.