By Sean Henahan, Access Excellence

BALTIMORE, Md. (1/2/97) A new type of experimental vaccine shows promise in protecting susceptible individuals from the perennial discomfort of cat allergy, suggests a study from Johns Hopkins University.

Image: 3-D structure of T-cell receptor

The new treatment is called an epitope vaccine. Molecular biologists cloned the cat dander allergen and identified specific T-cell epitopes associated with the human immune response. These developments coincide with increased understanding of the role of T-cells in the allergic response.

"Traditional allergy shots inject water and extracts from allergens like cat dander or pollen," says Phil Norman, M.D., professor of medicine. "This vaccine only injects very specific parts of cat allergens selected for their ability to favorably stimulate the immune system."

The research team gave 95 cat-allergic patients four injections of various levels of the vaccine or a placebo. Afterward, they were exposed to a room containing cats.

"Based on the patients' evaluation of their symptoms, the vaccine significantly reducing sneezing, itching, watery eyes and inflammation after a month of treatment," Norman says.

Traditional "allergy shots" involve the use of months worth of empirical hyposensitization with injected unstandardized allergenic extracts. The new epitope vaccines are injected subcutaneously in minute doses, and only once or twice. The early indications are that a single injection can provide prolonged protection against a specific allergen. The hope is that one or two injections would provide year round protection.

The traditional treatment also carries a risk of a serious allergic reaction. "In contrast, patients receiving the vaccine occasionally have mild symptoms on the injection day, but they require only simple treatment," Norman notes.

Vaccines are based on the idea that the proteins in allergens contain parts known as epitopes that stimulate the immune system. Separated from the rest of the protein, these epitopes interact with immune cells in a positive manner, causing a series of reactions that makes future allergic attacks less likely. But because the epitopes are given as a part of the whole protein in traditional allergy shots, the shots take a long time to work and sometimes trigger allergic reactions.

"If we're correct, this could make vaccines a superior approach for controlling many allergies," Norman says.

This epitope vaccine approach represents a new direction in allergy therapy. If successful, it will allow custom tailored anti-allergy treatments for a variety of common allergens, possibly with a single subcutaneous injection. If the vaccines work as the developers hope, the anticipated result would be prolonged T-cell down regulation, resulting in suppression of late phase allergic inflammation and IgE antibody synthesis.

The idea of using allergen extracts to treat allergies was first reported in 1911. It was originally thought that allergen extracts worked by raising blocking antibodies. In the 1970's this idea gave way to the concept that immunotherapy with allergen extracts worked by increasing suppressor T-cells which controlled IgE antibody production. The past decade has seen an explosion in the field of T-cell biology, which has taught much about the T-cell receptor and its interactions with antigen presenting cells. This led to the idea of creating T-cell epitopes to block IgE receptors, in turn blocking the allergic cascade.

Each allergen source (e.g. cats, ragweed) can have as many as 20 significant allergens, each with several T-cell epitopes. Researchers were initially skeptical that treatment with a restricted number of allergens or epitopes would be effective, particularly if the therapies involved recombinant allergens or synthetic peptides. However, several lines of evidence now suggest that one (in the case of cat allergy) or two (dust mite allergy) peptides are the dominant proteins for IgE antibody production.

Further studies also are planned to clarify how long the vaccine's effects last and how often follow-up injections are needed. If all goes well, Norman says, ALLERVAX CAT may be available in allergy clinics in several years. Early trials are also currently underway with a related ragweed allergy vaccine.

The study appeared in the December, 1996 issue of the American Journal of Respiratory and Critical Care Medicine.