Peptide Immunotherapy; Short but Long Lasting?

Opinion statement Allergen immunotherapy (AIT) with whole allergens or allergen extracts has been in use for more than one hundred years. It is clinically efficacious and disease-modifying. However, AIT is also associated with a profile of significant adverse events, including the potential to cause severe, systemic allergic reactions. One alternative to traditional whole-antigen AIT is peptide immunotherapy that uses small synthetic peptide immunoregulatory epitopes (SPIRE) representing T cell epitopes from the allergen of interest. Peptide immunotherapy is being developed for the treatment of allergic and autoimmune diseases where pathogenesis is T cell-dependent. Short, soluble, monomeric peptide fragments avoid the problem of IgE-mediated adverse events (since the peptides will not cross-link allergen-specific IgE on the surface of effector cells, such as mast cells and basophils). However, such peptides retain the ability to induce T cell tolerance and immunoregulation. In early clinical trials, efficacy was demonstrated months to years after the cessation of a short course of treatment, supporting the conclusion that this approach is disease-modifying, changing the natural history of the disease. The improved safety profile of short peptides allows for larger molar-equivalent doses to be administered in shorter time frames than AIT; treatment can be completed with as few as four intradermal injections, while efficacy persists for two years or more.