DNA Vaccines Fool the Immune System Into Fighting Itself - By Laurie Barclay, MD

Reviewed by Dr. Jacqueline Brooks

Aug. 2, 2000 -- Although the immune system normally protects against bacteria, cancer, and other marauders, it can turn against the body's own tissues, causing autoimmune diseases like rheumatoid arthritis and multiple sclerosis. Now, the findings of a study done on rats suggest that vaccines made from DNA may be able to fool the immune system into fighting itself -- thus preventing, and even treating, these diseases.

"As a nurse and a person with rheumatoid arthritis, I find the new research very exciting," Tina Underwood, 35, tells WebMD. "Each new advance brings us closer to the day when no one will have to live with the pain of rheumatoid arthritis. It gives me hope that my children or grandchildren may never have to experience the pain that I feel."

Like her maternal grandmother, who was diagnosed with rheumatoid arthritis in her early thirties, Underwood was found to have the disease in August 1996. Because of pain and immobility, she had surgery on eight joints in her right hand in October 1997, with good results.

The symptoms of rheumatoid arthritis are due to inflammation and swelling in the joints, brought on by chemicals that trigger an immune response in the body. These chemicals, called chemokines, attract white blood cells into the joint. The while blood cells, in turn, release substances that cause pain and swelling, and, eventually, cause the joint surfaces to wear down.

"Our strategy is to use [these so-called] naked DNA vaccines to re-educate the immune system to protect itself against its own harmful activities," study author Nathan Karin, PhD, an associate professor at the Bruce Rappoport Faculty of Medicine in Haifa, Israel, tells WebMD.

Karin and co-workers vaccinated rats with DNA genes that result in the formation of a specific chemokine and found that the rats generated antibodies blocking the effect of that chemokine, giving long-lasting protection from the destructive effects of arthritis. Their research was published in the Journal of Clinical Investigation.

By fooling the immune system into fighting only specific chemokines, these vaccines might someday prevent and treat rheumatoid arthritis and other autoimmune diseases without the side effects associated with currently available treatments.

"The past couple of years have brought us several new treatment options, but sadly, these have not been effective for everyone, and they are not without side effects," Underwood says. "I've experienced side effects to many drugs, ranging from mild to severe. The most annoying side effects were eight days of vomiting after my first dose of methotrexate, and the 'attractive' moon face and weight gain of prednisone."

Drugs that suppress the entire immune system, such as methotrexate or prednisone, may cause serious, even fatal, side effects by interfering with the production of blood cells in the bone marrow, leading to anemia, infections, and uncontrolled bleeding.

In theory, and after much more research in both animals and humans, an ideal DNA vaccine could target the symptoms of a particular autoimmune condition while leaving the rest of the bodily functions relatively unscathed.

"I think it is very important to weigh the potential side effects of a treatment against the potential benefits before making any decisions regarding treatment options," says Underwood, whose arthritis web page received the National Cecil Award from the Arthritis Foundation. "I don't worry too much about long-term side effects. My kids are still young, ages 10 and 11, and I want to be as active as I can now. If that means I am risking kidney disease or liver problems 20 years from now, I am aware of those risks and will deal with them when and if they occur."

Even a targeted DNA vaccine, no matter how specific, may also carry some risk. "A major concern for such a general approach ... is that the body's ability to combat infections during or immediately after the therapy with chemokine DNA vaccine may be severely compromised," says Kamal D. Moudgil, MD, PhD, who reviewed the study for WebMD.

"Nevertheless, this study represents an important advance in the ... treatment of autoimmune arthritis," says Moudgil, an associate professor of microbiology and immunology at the University of Maryland School of Medicine in Baltimore. "This should pave the way for developing more refined and disease-specific DNA vaccines."

Karin explains that other vaccines, made from antibodies, have been found to be helpful in rheumatoid arthritis clinical trials, but they are extremely expensive and inconvenient, as they have to be given weekly for life. An ideal DNA vaccine would be effective for longer periods of time and would fight autoimmune symptoms without affecting normal immunological functions. "We are fairly sure there will be some effect on immune system function, but much less than there is with [the drugs now used]," he says.

Karin estimates that clinical trials of a DNA vaccine for rheumatoid arthritis are at least 1 1/2 to 2 years away, and, depending on the results, many years may elapse before such a vaccine is widely available. So until better treatments are available, what should an arthritis patient do? "Educate yourself! Don't rely on your physician, nurse, or pharmacist to educate you," says Underwood. "It is YOUR body, it is YOUR responsibility to learn as much as you can. The more you know, the better able you are to deal with just about anything arthritis throws at you.

"Support groups, whether online or in real life, are a lifesaver," says Underwood, who hosts a chat group at www.arthritisinsight.com. "Fear is normal. You will be scared when you receive the initial diagnosis, and when you begin a new treatment or medication. Support and knowledge will help you overcome those fears."