Targeted DNA Vaccine May Reverse Autoimmune Disease
posted 08/25/03
May provide a way to reverse the course of such autoimmune diseases in humans as multiple sclerosis, rheumatoid arthritis and type-1 diabetes

Stanford University Medical Center researchers have developed a way to tailor therapies to combat the specific inappropriate responses of autoimmune diseases in mice. The researchers also have shown that their technique can provide information needed to predict a disease's progression. Eventually, their work may provide a way to reverse the course of such autoimmune diseases in humans as multiple sclerosis, rheumatoid arthritis and type-1 diabetes by first identifying the immune system culprits gone awry and then creating customized therapies for individual patients.

Autoimmune responses are thought to develop when antibodies attack many different proteins in the organ being targeted, so Robinson and his colleagues wanted to find a therapy that specifically knocked out as many of the harmful responses as possible while leaving the rest of the immune system functional. To do so, they took advantage of a well-known but poorly understood process known as tolerization. In this process, the immune system is coaxed to tolerate an offending protein after injection of that same protein or pieces of it. Utz, MD, assistant professor of medicine (immunology and rheumatology), likens the process to allergy shots: the agent causing the allergic reaction is injected into muscle in order for the body to learn to ignore it.

Using the microarray information to guide them to the targets of the autoimmune response in the sickest mice, Garren and Steinman, MD, professor of neurology and neurological sciences, built on previous studies in Steinman's lab to create a tolerizing vaccine that delivered four of the targeted proteins. To make an effective delivery vehicle, they put the DNA sequence that encoded the proteins into a circular piece of DNA called a plasmid, creating a DNA vaccine. When these engineered plasmids were injected, they produced the desired proteins and a programmed tolerization process began.

One advantage of DNA vaccines over other methods of tolerization, Garren noted, is that it allows for multiple autoimmune targets to be tolerized simultaneously rather than one at a time. "We found that this approach broadly turns off autoimmune responses," said Robinson. "Clinically, the animals do better when receiving the vaccine. When we use our arrays to monitor the response, we see broad reductions in the progression of the disease."

Led by Steinman, the team plans to use their findings to help people with autoimmune diseases. Using DNA vaccines to specifically turn off the immune system is a completely new way to immunize, said Steinman. "This is the opposite of what we try to do with traditional vaccines against bacteria and viruses, where we want to stimulate the immune system to attack the microbe," he added.

This study was funded by a number of sources, including funds from a $14.7 million contract from the National Institutes of Health, the Baxter Foundation and the Arthritis Foundation.

Source: Diabetes In Control Dot Com.

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