Recombinant allergens, peptides, and virus-like particles for allergy immunotherapy

Currently, extract-based therapeutic allergens from natural allergen sources (e.g., house dust mites, tree and grass pollen) are used for allergen-specific immunotherapy (AIT), the only causative therapy that can exhibit positive disease-modifying effects by tolerance induction and prevention of disease progression. Due to variations in the natural composition of the starting materials and different manufacturing processes, there are variations in protein content, allergen composition, and allergenic activity of similar products, which poses specific challenges for their standardization. The identification of the nucleotide sequences of allergenic proteins led to the development of molecular AIT approaches. This allows for the application of exclusively relevant structures as chemically synthesized peptides, recombinant single allergens, or molecules with hypoallergenic properties that potentially allow for an up-dosing with higher allergen-doses without allergic side effects leading more quickly to effective cumulative doses. Further modifications of AIT preparations to improve allergenic and immunogenic properties may be achieved, e.g., by including the use of virus-like particles (VLPs). To date, the herein described therapeutic approaches have been tested in clinical trials only. This article provides an overview of published molecular approaches for allergy treatment used in clinical AIT studies. Their added value and challenges compared to established therapeutic allergens are discussed. The aim of these approaches is to develop highly effective and well-tolerated AIT preparations with improved patient acceptance and adherence.