Genetic allergen modification in the development of novel approaches to specific immunotherapy

In the recent past, multiple allergens from relevant allergen sources have been cloned, sequenced and produced as recombinant proteins. The availability of recombinant allergens with immunological characteristics similar to their natural counterparts has improved the diagnosis of allergic disorders and increased our knowledge of the biochemical, structural and immunological characteristics of proteins with allergenic potential. Moreover, the use of defined recombinant proteins as vaccines substituting currently used total protein extracts from allergen sources may improve specific immunotherapy (SIT) of Type I allergy. In addition to producing well-defined batches of wild-type allergens, the recombinant technology offers the possibility to easily and selectively modify their properties or functions. Diverse modifications of allergens can be genetically engineered, e.g. variants with reduced IgE-binding capacity, multi-mers of single allergens or hybrids consisting of different allergens. Furthermore, allergens can be genetically fused with proteins that promote immune responses, which counterregulate the disease-eliciting T-helper type 2-dominated immune response in allergic individuals and may therefore, improve the efficacy of SIT. This review will introduce different concepts of allergen modification using genetic engineering to improve vaccines for SIT of Type I allergy.