Future directions for allergen immunotherapy.

Over the last 30 years several approaches to modify immunotherapy have been tested, including allergoids, alum precipitation, and most recently peptides. However, none of these have replaced the traditional regimens. Over the same period our scientific understanding of allergic disease has been transformed. Today it is possible to identify and monitor changes occurring during treatment and to target many different aspects of the immune system. Recombinant technology provides a powerful technique both for sequencing proteins and producing allergens in commercial quantities. The recombinant proteins can be modified by site-directed mutagenesis so as to decrease their reactivity with IgE antibodies while maintaining reactivity with T cells. Knowledge of the tertiary structure of allergens will make it simpler to identify and change surface epitopes. A completely different approach is to use plasmids to introduce the genes for an allergen. The strength of this technique is that the plasmid can be designed to control expression and also to influence the cytokine profile of the response or the isotype of antibodies produced. Finally, different adjuvants can be used with proteins to alter the response. These include IL-12, immunostimulatory sequences of DNA, and bacterial proteins such as those used in HibVax. It is now possible to identify the cells that control the immune response to allergens and to design treatments that will either downregulate or change the response of T cells. The challenge is to transform this information into an effective treatment for allergic disease.