By Sean Henahan, Access Excellence

SAN FRANCISCO- Synthetic epitope vaccines may be nothing to sneeze at for patients with common allergies including cat dander and ragweed, according to researchers at the American College of Allergy and Immunology.

Until recently, immunotherapy for patients with severe allergies involved the use of empirical hyposensitization with unstandardized allergenic extracts. Now, molecular biologists have cloned many major allergens 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.

The new vaccines are injected subcutaneously in minute doses. 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.

Researchers from the Johns Hopkins University School of Medicine conducted a double-blind placebo-controlled Phase III trial with an epitope vaccine developed from the cat dander allergen Fel d1. The vaccine consists of two 27 amino acid peptides derived from Fel d1.

A group of 72 patients with known cat allergy was randomized to receive one of three treatments. The first group received four weekly injections of 750 ug, a regimen which produced promising results in a Phase II study in which patients were locked in a room full of cats. The second groups received weekly escalating doses, beginning with 25 ug, while a third group received placebo.

The researchers measured forced expiratory volume, a commonly used test to assess bronchial function in asthmatics, prior to receiving the cat allergen vaccine and again at one week and six weeks after treatment.

A majority of patients, 71%, showed improvements. In contrast, no significant improvement was observed in the escalating dose group or in the placebo group. Side effects were allergic in nature, and were mild and transitory. A follow-up study of participants in an earlier phase II studies showed that 75% of patients receiving 750 ug injections maintained some or all benefit after seven and a half months.

"The bronchial challenge trial results demonstrate that the peptides were well tolerated and that they do modify bronchial responses to cat allergen," reported Peter Creticos, M.D., Associate Professor of Medicine, Johns Hopkins University School of Medicine.

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, notes Dr. Thomas Platts-Mills, Head, Division of Allergy and Immunology, University of Virginia Asthma and Allergic Disease Center.

The development of novel approaches to the treatment of allergy such as synthetic T-cell peptides offers the potential of avoiding the risks associated with conventional allergen extracts including side effects and anaphylaxis, he said.

Cat allergy is more than just a significant cause of discomfort to millions of people worldwide. Common allergies including cat and house dust mite are now implicated as triggers of asthma attacks. Current asthma treatment guidelines from the WHO call for aggressive reduction in allergen exposure to patients, as well as comprehensive medical management.

Transmitted: 95-03-07 19:04:43 EST

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