April 3, 2000
For years, efforts to develop improved vaccines for asthma and allergies have been thwarted because the vaccines themselves often cause the very symptoms a person is trying to avoid. Research efforts have been aimed at attempting to improve efficacy, increase safety, decrease treatment time and improve compliance. Now, at a recent conference, researchers at Johns Hopkins, the University of California at San Diego, and Dynavax Technologies Corporation announce that they have developed a method of modifying an allergen, such as ragweed, to create a vaccine that may solve many of these concerns.
"Our first experience of testing this new vaccine approach in ragweed-allergic people supports the hypothesis that this novel vaccine may provide a safer and potentially more effective therapeutic vaccine for allergic diseases," says Peter S. Creticos, M.D., an associate professor of medicine at Johns Hopkins.
Creticos reports the new research at the 15th Annual Update of Frontiers in Research and Clinical Management of Asthma and Allergy held March 31 through April 2 in Baltimore.
People suffer allergic reactions when their immune systems overreact to an allergen such as ragweed pollen. The allergen typically induces certain immune cells, including the type 2 helper T cells (Th2), to produce a variety of biochemicals responsible for the allergy sufferers' miseries.
To combat these reactions, doctors traditionally have injected an individual with a vaccine containing the allergen that is causing them trouble. Injecting an allergen apparently causes the body to produce less Th2 than what would occur if a person were to encounter the allergen naturally. These vaccines cause the body to produce allergen-attacking antibodies. Through a series of these vaccinations, which to the body are like handicapped fights, the immune system learns how to defend itself and becomes a better fighter when the real agent attacks. Some vaccines, however, cannot be tolerated by individuals because the antigen in the vaccine is so strong that, even when injected, it elicits a potent allergic reaction.
To create a more tolerable vaccine, the researchers realized that they must "mask" the allergic sites on the allergen molecule. They discovered that this could be accomplished by attaching a specific, short sequence of synthetic DNA to the relevant allergen. Researchers have shown that this DNA sequence can induce the body to produce protective molecules, type 1 helper T cells (Th1). Th1 cells inhibit the pro-inflammatory Th2 cells responsible for the allergic inflammatory reaction.
"In animal studies and in laboratory tests with human cells, this approach has been shown to be very effective in terms of being able to generate immunity," says Lawrence Lichtenstein, M.D., Ph.D., a professor of clinical immunology at Johns Hopkins who is involved in the new research.
Now, Creticos reports the results of the first human studies with this novel modified vaccine, named AIC. In the new study, six ragweed-allergic volunteers underwent skin testing in a blinded fashion with both ragweed and AIC. Skin testing is a way of measuring redness and swelling to determine the allergic response produced by an allergen, in this case ragweed. The researchers found that the new AIC product was 180 times less allergenic than a licensed product. This preliminary clinical experiment confirms the results of the previous animal work and human blood test work. The researchers hope to begin phase I clinical efficacy trials in the near future.
The study was sponsored by Dynavax Technologies Corporation. Lichtenstein serves on Dynavax's Scientific Advisory Board and owns Dynavax stock, which is subject to certain restrictions under Johns Hopkins policy. Creticos is a scientific consultant to the company. The terms of this arrangement are being managed by the university in accordance with its conflict of interest policies.