By Sean Henahan, Access Excellence
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
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
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
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