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.