Toll-like receptor 5 ligand based vaccines for prophylactic and therapeutic intervention of IgE-mediated allergies

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Although allergen-specific immunotherapy (SIT) using crude allergen extracts is established for certain inhalant allergies, only few patients undergo SIT. SIT still possess the risk of severe unwanted side effects and is currently not available for the treatment of food allergies. In order to increase efficacy, safety and compliance, novel vaccination strategies are required. Novel approaches for the prevention of IgE-mediated allergies will combine recombinant allergens and adjuvants, e.g. immune modulation facilitated by pathogen-associated molecular patterns. The project will explore whether recombinant fusion proteins, consisting of TLR5-ligand flagellin flaA and allergens, may be effective vaccine candidates for food allergies. Immune modulating properties of the flaA-allergen fusion proteins, in comparison to the mixture of flaA and allergen, will be evaluated in vitro and in vivo using wild-type and knock-out mice. In vitro studies using differentiated bone marrow derived dendritic cells (BMDC) and co-cultured with allergen specific CD4+ T cells will be addressed to elucidate the mechanism of the immune modulation. Prophylactic and therapeutic vaccination will be evaluated in appropriate mice models in regard to symptoms, and the modulation of the innate and adaptive immune responses. The proposed study will provide information regarding the safety and efficacy of potential TLR5-ligand based vaccines for the intervention of allergies.