Molecular Translational Allergology

Since the first trials by Noon and Freeman, allergen-specific immunotherapy (AIT) has become the approach of choice targeting the underlying mechanisms of allergic disorders for the management of these diseases by modifying the course of the disease. To date, AIT represents the only disease modifying curative treatment of allergy, whereby venom-specific immunotherapy (VIT) is one of the most effective treatments in the field of clinical allergology. However, the mechanisms of AIT are not understood in detail. As venom allergy may arise independent of the atopic status, it remains the best model to understand the mechanisms of allergy and immune tolerance even in non-atopic individuals. Additionally, venom immunotherapy represent an excellent model to study the cellular and molecular mechanisms of immune tolerance development in sensitized individuals, whereas high-dose bee venom exposure in beekeepers by natural bee stings represents a model to understand the mechanisms of tolerance to allergens in healthy individuals.

Therefore, our projects aim to deeply characterize the immune status of patients undergoing immunotherapy as well as of beekeepers, naturally exposed to the allergen source. Aim is to better understand the immunological mechanisms that contribute to natural occurring tolerance as well as to the success of AIT in allergic individuals. The understanding of these mechanisms might also allow identifying useful biomarkers for the prediction of the success of AIT.

Allergies to airborne allergens are dramatically rising in industrialized countries. Specific immunotherapy is the only curative treatment of allergic diseases which is able to induce long-term tolerance in allergic individuals. However, success rates vary and are particularly low e.g. for the treatment of house dust mite (HDM) allergy. We are using different in vivo models of acute and chronic allergic asthma as well as of allergen-specific immunotherapy to study the mechanisms of disease and therapeutic intervention.  On the one hand these models allow gaining deep insights into the immunological mechanisms of sensitization, disease and therapeutic intervention and on the other hand to study the efficacy of novel therapeutics and adjuvants and, therefore, the development of advanced therapeutic approaches with translational potential.

The aim of different projects is the identification, characterization and engineering of allergens with a focus on Hymenoptera venom allergy.

On the one hand these allergens build the basis for novel component-resolved diagnostic approaches. Choosing the correct venom for allergen-specific immunotherapy represents a crucial prerequisite for effective protection against severe and even fatal anaphylactic sting reactions. In the past, therapeutic decisions based on specific IgE levels to whole venom extracts were not always straightforward due to cross-reactivity between different venoms caused by the presence of homologous allergens and cross-reactive carbohydrate determinants (CCDs). The knowledge of the composition of Hymenoptera venoms regarding relevant allergens rapidly increases. Analyses using recombinant CCD-free allergens allow their detailed characterization and the identification of novel relevant venom allergens. These allergens can build the pillars of component-resolved diagnostics which has demonstrated high potential for better patient care. In the future, sensitization profiles of patients might even more direct therapeutic decisions in a personalized and patient-tailored manner.

On the other hand our projects focus on the identification of T and B cell epitopes of important allergens and, hence, on the understanding of the molecular mechanisms of interaction between allergens and different parts of the immune system. Moreover, these analyses build the basis for the engineering of allergen molecules for novel advanced immunotherapeutic strategies.

Although specific immunotherapy in many cases represents an effective treatment, therapy failures happen and patient compliance is low due to long treatment times. Our goal is the development of novel immune modulators and local application forms to find an effective and long lasting cure for immune diseases. For shifting immune balance from a state of disease to a tolerogenic state we combine the allergen-specific immunotherapy with immune modulators to support the induction of tolerogenic pathways. Moreover, we are developing strategies for the local application of the active substances to create a tolerogenic microenvironment at the site of allergen presentation.