Furthermore, each of these peptides was shown to induce Bet v 1-specific IgG antibodies upon immunization, which strongly inhibited birch pollen allergic patients’ IgE binding to the allergen (i.e. immunized with the peptide vaccine before or after sensitization to Bet v 1. Bet v 1- and peptide-specific antibody responses were analysed by ELISA. T cell and cytokine responses to Bet v 1, KLH, and the peptides were studied in proliferation assays. The effects of peptide-specific and allergen-specific antibodies on T cell responses and allergic lung inflammation Zofenopril calcium were studied using specific antibodies. == Results == Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides induced a Bet v 1-specific IgG antibody response without priming/boosting of Bet v 1-specific T cells. Prophylactic and therapeutic vaccination of mice with the peptide vaccine induced Bet v 1-specific antibodies which suppressed Bet v Zofenopril calcium 1-specific T cell responses and allergic lung inflammation. == Conclusion and Clinical Relevance == Vaccination with carrier-bound allergen-derived peptides lacking allergen-specific T cell epitopes induces allergen-specific IgG antibodies which suppress allergen-specific T cell responses and allergic lung inflammation. Keywords:allergens, allergy vaccination, peptides, specific immunotherapy == Introduction == Recently, a strategy for the development of safe allergy vaccines has been developed (reviewed in1), which is based on the hapten-carrier theory2,3. According to this concept, allergen-specific IgG antibody responses can be obtained by immunization with Zofenopril calcium allergen-derived peptides which are either chemically bound to a carrier molecule or linked to the carrier in the form of a recombinant fusion protein1,4. The T cell help for the production of allergen-specific IgG antibodies is usually obtained from a carrier molecule. The allergen-derived peptides in the vaccines are derived from areas of allergens made up of IgE binding sites, but themselves lack IgE reactivity, allergenic activity (i.e. ability to cross-link mast cell-or basophil-bound IgE) and allergen-specific T cell epitopes512. Allergy vaccines that are based on such carrier-bound allergen-derived peptides should induce allergen-specific IgG antibodies which block IgE-mediated allergic inflammation Zofenopril calcium and allow reducing IgE- as well as T cell-mediated side-effects during SIT1. It has been shown that immunization of animals (i.e. mice, rabbits) with carrier-bound allergen-derived peptides from several major allergens (i.e. timothy grass pollen allergen, Phl p 1, birch pollen allergen, Bet v 1, cat allergen, Fel d 1, olive pollen allergen, Ole e 1, house dust mite allergen, Der p 2, mould allergen, Alt a 1) which lacked IgE reactivity and allergenic activity induced allergen-specific IgG antibodies that inhibited allergic patients’ IgE binding to the allergen and allergen-induced basophil activation611. Thus, the major immunological mechanism underlying carrier-bound allergen-derived peptide vaccines seems to be the induction of allergen-specific IgG blocking antibodies which may inhibit IgE-mediated mast cell and basophil degranulation and thus immediate allergic inflammation13,14. However, it is possible that allergen-specific IgG antibodies induced by SIT may also block boosts of allergen-specific IgE production1517and eventually allergen-specific T cell activation. Support for the latter mechanism comes from the demonstration that SIT-induced allergen-specific IgG can block Zofenopril calcium IgE-facilitated allergen presentation to T cells and thus T cell activationin vitro18,19. Here, we established anin vivomouse model to investigate whether prophylactic and Rabbit Polyclonal to 5-HT-3A therapeutic vaccination with carrier-bound allergen-derived peptide vaccines lacking allergen-derived T cell epitopes can influence allergen-specific T cell responses. As model allergen, we used the major birch pollen allergen, Bet v 120, which contains most of the IgE epitopes present in tree pollens belonging to the orderFagales(birch, alder, hazel, oak) and is responsible for oral allergy syndrome to plant-derived food (e.g. apple, nuts, carrot)21,22. A peptide vaccine was formulated with carrier-bound Bet v 1-derived peptides lacking allergenic activity and T cell epitopes, and it was studied whether prophylactic and/or therapeutic vaccination of mice influences allergen-specific T cell responses. == Methods == == Allergens, peptides, KLH-coupled peptide vaccine == Purified recombinant Bet v 1 was purchased from Biomay AG (Vienna, Austria). Six Bet v 1-derived peptides of approximately 30 aa length spanning the Bet v 1 sequence (Fig.1) were synthesized using the 9-fluorenylmethoxycarbonyl (Fmoc) strategy with 2-(1H-Benzotriazol-1-yl) 1,1,3,3 tetramethyluronium hexafluorophosphat (HBTU) activation (0.1 mmsmall-scale cycles) on.