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Research Type I allergies are hypersensitivity reactions of the immune system to harmless substances (allergens). Allergic diseases such as allergic rhinoconjunctivitis, atopic asthma and atopic dermatitis affect more than 20% of the population in Austria and other industrialized countries. This high prevalence demands for highly efficient and safe therapeutic interventions.
Allergen-specific
T lymphocytes play a central role in Type I allergies. In
allergic individuals the T cell response to allergens is dominated
by so-called T helper (h) 2 cells. Th2 cells produce high amounts of
interleukin-4 and interleukin-13, cytokines that induce the
production of allergen-specific IgE antibodies. Allergic symptoms
such as rhinoconjunctivitis are caused by allergen-specific
IgE-mediated processes. Moreover, allergen-specific T cells are
involved in inflammatory late phase responses in target organs, such
as the skin or the lung. Therefore,
the downregulation of the overwhelming, disease-eliciting Th2
response in allergic individuals is an important aim of therapeutic
interventions to cure allergy.
Specific
immunotherapy
(SIT) is the only causative treatment for Type I allergy that
downregulates the disease-eliciting allergen-specific Th2 response.
SIT consists in the repeated administration of increasing doses of
allergens to the patient in order to achieve clinical tolerance to
natural allergen exposure. At present, vaccines used for SIT consist
of protein extracts of allergenic sources, e.g. birch pollen extract.
These crude extracts are a mixture of allergens and non-allergenic
proteins. Their content and quality strongly depends on the
production process and may vary from batch to batch and from company
to company. Recombinant allergens, i.e. single proteins with
known biological and immunological activity and standardizable
quantity, can overcome the disadvantages of crude allergen extracts.
Another advantage of recombinant allergens is the possibility to
alter their features by genetic engineering. For example,
hypoallergenic variants, i.e. allergens with no/low IgE-binding and
retained T cell activating capacity, can be engineered. Watch
a movie
summarizing the advantages of recombinant allergens over natural
allergen extracts.
The
major aims of the Christian Doppler Laboratory for
Immunomodulation are to modulate or block T cell-dependent
phases of the allergic immune response by vaccines that specifically
target allergen-specific T lymphocytes. The research in Module 1-3
aims at the development of recombinant allergen-modulator conjugates
that counter-regulate the allergen-specific Th2 response and show
reduced IgE-mediated side effects. Module 4 aims at the
production of molecules that directly block the activation of
allergen-specific T cells.
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