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.
KeywordsAllergy Clin Immunol Cell Epitope Allergen Challenge Allergen Immunotherapy Late Asthmatic Reaction
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- 1.Floistrup H, Swartz J, Bergstrom A, Alm JS, Scheynius A, van HM, Waser M, Braun-Fahrlander C, Schram-Bijkerk D, Huber M, Zutavern A, von ME, Ublagger E, Riedler J, Michaels KB, Pershagen G. The Parsifal Study Group. Allergic disease and sensitization in Steiner school children. J Allergy Clin Immunol 2006; 117:59–66CrossRefPubMedGoogle Scholar
- 2.Akdis M, Verhagen J, Taylor A, Karamloo F, Karagiannidis C, Crameri R, Thunberg S, Deniz G, Valenta R, Fiebig H, Kegel C, Disch R, Schmidt-Weber CB, Blaser K, Akdis CA. Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med 2004; 199:1567–75CrossRefPubMedGoogle Scholar
- 4.Moller C, Dreborg S, Ferdousi HA, Halken S, Host A, Jacobsen L, Koivikko A, Koller DY, Niggemann B, Norberg LA, Urbanek R, Valovirta E, Wahn U. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol 2002; 109:251–6CrossRefPubMedGoogle Scholar
- 15.Lichtenstein LM, Ishizaka K, Norman PS, Sobotka AK, Hill BM. IgE antibody measurements in ragweed hay fever. Relationship to clinical severity and the results of immunotherapy. J Clin Invest 1973; 52:472–82Google Scholar
- 16.Durham SR, Ying S, Varney VA, Jacobson MR, Sudderick RM, Mackay IS, Kay AB, Hamid QA. Grass pollen immunotherapy inhibits allergen-induced infiltration of CD4+ T lymphocytes and eosinophils in the nasal mucosa and increases the number of cells expressing messenger RNA for interferon-gamma. J Allergy Clin Immunol 1996; 97:1356–65CrossRefPubMedGoogle Scholar
- 19.Ebner C, Siemann U, Bohle B, Willheim M, Wiedermann U, Schenk S, Klotz F, Ebner H, Kraft D, Scheiner O. Immunological changes during specific immunotherapy of grass pollen allergy: reduced lymphoproliferative responses to allergen and shift from TH2 to TH1 in T-cell clones specific for Phl p 1, a major grass pollen allergen. Clin Exp Allergy 1997; 27:1007–15CrossRefPubMedGoogle Scholar