Josef Thalhamer

Due to the increasing prevalence of type I allergy, there is an urgent need for novel therapeutic but also prophylactic approaches against this disease. We have long lasting experience in the field of intradermal genetic immunization and have demonstrated the proof of concept for tailor-made allergy vaccines based on plasmid DNA and messenger RNA. The optimal safety profile makes RNA a promising candidate for a first human prophylactic vaccine for early protection against allergic sensitization. While prophylaxis may be the most efficient intervention, the high incidence of allergic diseases calls for improved therapeutic vaccines. Allergen specific immunotherapy suffers from low patient compliance due to the need for a multitude of subcutaneous injections over several years and the risk of systemic side effects.

The skin has been rediscovered as an effective route for vaccination, not only for gene vaccines but also for protein vaccines. It is rich in antigen presenting cells and is efficiently drained via local lymph nodes. We have recently established transcutaneous immunotherapy via laser-generated micropores, which displays similar efficacy compared to subcutaneous immunization. Using glycoconjugates of allergens and carbohydrates, we design nanoparticles with decreased allergenicity (so-called hypoallergens) and increased immunogenicity, which specifically target skin dendritic cells via different receptors.

These translational research approaches are based on studies of cellular and molecular mechanisms of skin immunity, with a focus on immune polarization and allergic sensitization. Currently, we use state-of-the-art transgenic mouse models to investigate immune functions of epidermal Langerhans cells by inducible antigen expression after genetic immunization, and the influence of structural stability of proteins on immunogenicity and immune response polarization using in silico mutation and screening approaches followed by wet lab analysis.

Contact

Josef Thalhamer
Department of Biosciences
Faculty for Natural Sciences
Hellbrunner Straße 34
5020 Salzburg

+43 662 8044 5737
josef.thalhamer@sbg.ac.at
http://www.uni-salzburg.at/thalhamer
 0000-0003-2285-6400
 E-5787-2011

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