Concepts and perspectives on peptide-based immunotherapy in allergy

Allergen-specific T cells play a key role in the pathogenesis of allergic diseases through provision of help for allergen-specific B cells and control of inflammatory responses. Allergen immunotherapy using intact allergen proteins (given either subcutaneously or sublingually) is clinically effective and demonstrates enduring efficacy (i. e., disease modifying). However, the requirement for monthly injections or daily sublingual administration (both for 3 years), combined with a high frequency of local and systemic adverse events, results in poor compliance. Targeting allergen-specific T cells with synthetic peptides representing dominant T cell epitopes markedly decreases treatment times (4–8 intradermal injections), reduces adverse events and provides efficacy for at least 2 years. We have developed peptide immunotherapies for allergies triggered by cats, house dust mites, and grass pollen.Each of these consists of a mixture of seven peptides containing multiple dominant T cell epitopes and each have demonstrated statistically significant improvements in rhinoconjunctivitis symptom scores in controlled allergen challenge facilities. The mechanisms of action appear to involve increased IL-10 production, intra- and inter-molecular suppression, and down-regulation of chemokine pathways. In contrast, treatment does not appear to be associated with deletion of allergen-specific T cells, nor with the induction of allergen-specific IgG (as is seen with conventional whole allergen immunotherapy).