Sublingual immunotherapy: from biological extracts to recombinant allergens

Sublingual vaccines based on biological extracts from various natural allergen sources are effective in the treatment of respiratory allergies. These vaccines comprise a complex mixture of proteins and glycoproteins that require dedicated standardization procedures to ensure batch-to-batch consistency. Because of the lack of correlation between the potency of an allergen extract and the quantity of major allergen content, standardization is achieved predominantly by determining the global IgE binding capacity of the extract in vitro. New proteomic technologies can be used to further characterize the most abundant proteins present in an extract. Second-generation sublingual vaccines based on recombinant allergens are under development. The aim is to produce molecularly defined vaccines that exhibit superior efficacy, while allowing for simplified immunization schedules. In this approach, recombinant DNA technology is used to express highly purified allergens in their native (i.e. wild-type) conformation. The recombinant allergens are then formulated with ad hoc adjuvants and/or mucoadhesive galenic excipients so that they specifically target oral Langerhans cells and induce allergen-specific regulatory T cells.