Research Topics

Figure 1Description of the specific research topics
Figure 1 gives an overview of the different research topics 1-3 of the SFB. The numbers of those projects which will collaborate with each other and will make major contributions to the individual topics are indicated. A detailed description of the individual project parts and of the collaborations which are planned in the SFB to achieve the common goals can be found in the description of the individual project parts (see: 3. Research Program-Description of the project parts: Position within the SFB, internal collaborations). The groups participating in this SFB program have already established intensive collaborations which are documented by a large number of common publications. The applicants have identified earlier publications resulting from the collaboration with groups involved in this SFB in their publications lists (see: List of publications 2006-2011) in their CVs which they have attached to their individual project parts (see: 3. Research Program-Description of the project parts)

 

 

Topic 1: Characterization of allergens for vaccine development.
In topic 1 projects  02, 03, 04, 05 and 06 will work closely together to develop therapeutic and prophylactic vaccines for defined and clinically relevant allergens. An important task will be the identification of the clinically most relevant allergens which need to be included in allergen-specific forms of treatment. In a first step allergens will be produced by recombinant expression and compared regarding fold and immunological properties with the natural wildtype allergens in collaborations with those groups who have experience in the structural analysis of allergens (project 04) and groups working with allergen-specific antibodies (project 07), patients cells (projects 08, 10, 11, 13, 14, 15) and those using animal models (projects 05, 06, 09, 12). The frequency of IgE recognition and the allergenic activity of the allergens will be determined in collaboration with projects using cellular assays and in vivo provocation tests 08, 10, 11, 13, 14, 15. The work carried out in topic 1 should thus identify those allergens which need to be included in specific treatment and prophylactic therapy strategies. Projects 07, 08, 09 and 10 will utilize the allergen models pursued in this topic so that there will be tight collaborations between the groups with molecular and cellular approaches. Allergens, their epitopes and allergen derivatives characterized in topic 1 will be also used in topics 2 and 3 as clinically relevant models and thus ensure a close interaction between all research groups.

Topic 2: Development of diagnostic, therapeutic and prophylactic strategies
Projects 02, 03, 04, 07 and 11 will collaborate regarding the development of multiallergen/epitope test systems reading humoral and cellular allergen-specific immune responses. The diagnostic test systems will be useful to identify major and minor allergens and can be used for the selection of suitable patients for immunotherapy, for the monitoring of immune responses in the planned animal models (projects 05, 06, 07, 12) and for studying immune responses in vaccination/tolerance induction studies in humans (projects 05, 15). Project 08 will analyze allergen/derivative-specific DC gene signatures. Projects 05, 10, and 15 want to study also “normal” immune responses associated with protection and/or tolerance.
For therapy and prophylaxis several different molecular approaches (e.g., recombinant hypoallergens, carrier-bound allergen peptides, mimotopes, self-adjuvanted molecules) will be pursued by projects 02, 03, 04, 05, 06, 07, 08, 10, 12) in topic 2. In addition, allergen-specific antibodies (project 6), cellular approaches (projects 08, 09, 11, 13, 14) and adjuvant approaches (projects 10, 12) will be developed in topic 2. The SFB group will be able to work with defined clinically relevant allergens (topic 1)in their cellular and in vivo models.  

Topic 3: Mechanistic in vitro and in vivo studies for evaluation of therapeutic and prophylactic concepts
The translation of therapeutic and prophylactic concepts into clinical use requires preclinical research at several levels. Cultivated cells and tissues from patients will be used to study in vitro properties of vaccine candidates and adjuvants. Almost all projects will use common in vitro systems based on human cells from allergic patients with clinically well-defined symptoms and non-allergic individuals (projects 02, 03, 05-15) (e.g., PBMC, basophils, APCs, T cell lines/clones) for the analysis of vaccine candidates and other therapeutic strategies developed in topic 2. In addition, tissue-specimens and other more sophisticated culture systems (e.g., cultured respiratory, intestinal epithelial cells and skin-derived cells) will allow groups producing molecular and cellular therapeutic approaches to test these in in vitro surrogate systems (e.g., prevention of allergen penetration through cultured respiratory cells) together with clinical research groups.
Another important pre-requisite for the evaluation of therapeutic and prophylactic strategies into clinical use is testing in suitable animal models which are closely connected to human disease. There are substantial differences between the immune system of allergic patients and various animals, but certain questions can be well studied in animal models. For example, it has turned out to be useful to test, whether certain allergen derivatives can induce protective antibodies which recognize the wild type allergen or prevent allergic patients IgE binding to the allergen (31, 32). Furthermore, it can be studied whether certain treatments induce allergic sensitization or tolerance or protective immune responses. For basic mechanistic and safety considerations, the latter experiments must be performed before molecules or strategies can be investigated in humans. The use of murine and canine models for respiratory, skin and food allergy (projects 06, 12, 14) as well as double transgenic mice expressing human allergen-specific T cell receptors and human MHC (project 09) which have been and will be developed by the applicants will therefore be important for the evaluation of therapeutic and prophylactic approaches before proceeding to investigations in humans.
The involvement of research groups with clinical expertise (projects 13, 14, 15) will allow to perform research directly in patients with various forms of allergy (respiratory, skin, intestinal) as well as in paediatric populations.