Towards the development of prophylactic allergy vaccines

Type I allergy is an IgE-mediated hypersensitivity disease which affects more than 25% of individuals in industrialized countries. In untreated patients the disease progresses frequently from mild symptoms (e.g., rhinoconjunctivitis) to severe and chronic manifestations (e.g., asthma bronchiale). Therapeutic vaccination with the disease-eliciting allergens represents a causative treatment, which prevents the progression of the disease but can only be administered to a small group of selected patients because of the risk of allergenic side effects and the poor quality of allergen extracts. In a previous FWF project we have developed by recombinant DNA technology and peptide chemistry derivatives of birch and grass pollen allergens with reduced allergenic activity. Furthermore, we demonstrated in a clinical immunotherapy study that birch pollen allergy can be treated with the major birch pollen allergen, Bet v 1. Using the previously developed recombinant hypoallergenic Bet v 1 derivatives the current project aims to develop a novel concept for prophylactic allergy vaccination. In a small clinical feasibility trial, the immunological mechanisms underlying vaccination of healthy individuals with hypoallergenic Bet v 1-derivatives will be investigated. In parallel, it is planned to develop and evaluate carrier molecules for vaccination with allergen-derivatives. This project should deliver evidence for the feasibility of prophylactic allergy vaccination with recombinant hypoallergenic allergen derivatives. Furthermore, therapeutic human antibodies from vaccinated individuals will be gnerated and carrier molecules for improved allergy vaccination will be developed. With this project we hope to open a novel avenue for prophylactic allergy vaccination.

More than 25% of the population suffers from IgE antibody-mediated allergies. In untreated patients the disease tends to progress from mild symptoms (e.g., rhinoconjunctivitis) to severe and often disabling manifestations (e.g., asthma). Allergen-specific immunotherapy, the only disease-modifying treatment is based on the administration of the disease-causing allergens to patients but suffers from several disadvantages. Currently used allergen-extract are of poor quality and may induce severe side effects. Furthermore, allergen-specific immunotherapy can be only given as therapeutic vaccine because administration of naturally occurring allergens may induce allergic sensitization. In this project we started to explore if genetically engineered derivatives of the major birch pollen allergen, Bet v 1, may be used for prophylactic vaccination and developed recombinant carrier molecules derived from viruses and bacteria which might be useful for the development of prophylactic allergy vaccines. In small clinical studies we have obtained evidence that recombinant Bet v 1 derivatives do not augment or induce allergic sensitization. Furthermore, we developed several carrier-molecules derived from viruses and bacteria which can be fused with allergen-derived peptides to obtain prophylactic allergy vaccines that induce protective immune responses, both against the allergen and against viral infection. The results obtained in our study suggest that it may be possible to develop allergy vaccines which may be used for the prevention of allergies.