Peptide-Based Therapeutic Vaccines for Allergic Diseases: Where Do We Stand?

In healthy individuals, the immune system is regulated by a variety of mechanisms, which ensure that balance is maintained between inflammatory and anti-inflammatory responses. The diverse repertoire of antigen-specific lymphocytes harbours the potential for the recognition of self, as well as pathogen-derived epitopes and innocuous environmental antigens. In healthy individuals, lymphocyte reactivity is controlled by the central and peripheral tolerance mechanisms. In allergic and autoimmune conditions, however, inappropriate responses are generated as peripheral regulatory mechanisms fail. Disease-modifying therapeutic strategies aim to re-establish homeostasis between effector and regulatory responses. This has been successfully accomplished through allergen-specific immunotherapy (SIT). Despite the clinical efficacy of this form of therapy, it is associated with frequent and potentially life-threatening adverse events which arise primarily as a result of the allergenicity of the treatment preparation. Several strategies to reduce the allergenicity of this form of treatment, whilst maintaining clinical efficacy, are under development. Peptide immunotherapy is one such approach in which synthetic peptides targeting T cell epitopes of the allergen are administered to allergic subjects. Clinical studies have confirmed findings in experimental models, demonstrating the induction of allergen-specific immunological tolerance. The clinical consequences of tolerance induction are discussed herein.