BACKGROUND: More than 90% of house dust mite-allergic patients are sensitized to the major Dermatophagoides pteronyssinus allergen, Der p 2. The aim of this study was to develop and characterize an allergy vaccine based on carrier-bound Der p 2 peptides, which should allow reducing IgE- and T-cell-mediated side-effects during specific immunotherapy (SIT). METHODS: Five Der p 2 peptides (P1-P5) were synthesized and analyzed regarding IgE reactivity and allergenic activity. Lymphoproliferative and cytokine responses induced with Der p 2 and Der p 2 peptides were determined in peripheral blood mononuclear cells from mite-allergic patients. Der p 2-specific IgG antibodies induced with carrier-bound Der p 2 peptides in mice and rabbits were tested for their capacity to inhibit IgE binding and basophil activation in allergic patients. RESULTS: Of five overlapping peptides (P1-P5) covering the Der p 2 sequence, two peptides (P2 and P4) were identified, which showed no relevant IgE reactivity, allergenic activity, and induced lower Der p 2-specific T-cell activation than Der p 2. However, when coupled to a carrier, P2 and P4 induced Der p 2-specific IgG antibodies in animals, which inhibited allergic patients' IgE binding to the allergen and allergen-induced basophil activation similar as antibodies induced with Der p 2. CONCLUSIONS: Carrier-bound Der p 2 peptides should allow avoiding IgE-mediated side-effects, and because of their low potential to activate allergen-specific T cells, they may reduce late-phase side-effects during SIT. Further, these peptides may be also useful for prophylactic vaccination.
BACKGROUND: More than 90% of house dust mite-allergic patients are sensitized to the major Dermatophagoides pteronyssinus allergen, Der p 2. The aim of this study was to develop and characterize an allergy vaccine based on carrier-bound Der p 2 peptides, which should allow reducing IgE- and T-cell-mediated side-effects during specific immunotherapy (SIT). METHODS: Five Der p 2 peptides (P1-P5) were synthesized and analyzed regarding IgE reactivity and allergenic activity. Lymphoproliferative and cytokine responses induced with Der p 2 and Der p 2 peptides were determined in peripheral blood mononuclear cells from mite-allergic patients. Der p 2-specific IgG antibodies induced with carrier-bound Der p 2 peptides in mice and rabbits were tested for their capacity to inhibit IgE binding and basophil activation in allergic patients. RESULTS: Of five overlapping peptides (P1-P5) covering the Der p 2 sequence, two peptides (P2 and P4) were identified, which showed no relevant IgE reactivity, allergenic activity, and induced lower Der p 2-specific T-cell activation than Der p 2. However, when coupled to a carrier, P2 and P4 induced Der p 2-specific IgG antibodies in animals, which inhibited allergic patients' IgE binding to the allergen and allergen-induced basophil activation similar as antibodies induced with Der p 2. CONCLUSIONS: Carrier-bound Der p 2 peptides should allow avoiding IgE-mediated side-effects, and because of their low potential to activate allergen-specific T cells, they may reduce late-phase side-effects during SIT. Further, these peptides may be also useful for prophylactic vaccination.
Authors: V Niederberger; F Horak; S Vrtala; S Spitzauer; M-T Krauth; P Valent; J Reisinger; M Pelzmann; B Hayek; M Kronqvist; G Gafvelin; H Grönlund; A Purohit; R Suck; H Fiebig; O Cromwell; G Pauli; M van Hage-Hamsten; R Valenta Journal: Proc Natl Acad Sci U S A Date: 2004-08-13 Impact factor: 11.205
Authors: Dubravka Smiljkovic; Renata Kiss; Christian Lupinek; Gregor Hoermann; Georg Greiner; Nadine Witzeneder; Gerhard Krajnik; Franz Trautinger; Susanne Vrtala; Irene Mittermann; Michael Kundi; Bernd Jilma; Rudolf Valenta; Wolfgang R Sperr; Peter Valent Journal: J Allergy Clin Immunol Pract Date: 2020-04-26
Authors: Carla Oseroff; Lars H Christensen; Luise Westernberg; John Pham; Jerome Lane; Sinu Paul; Jason Greenbaum; Thomas Stranzl; Gitte Lund; Ilka Hoof; Jens Holm; Peter A Würtzen; Kåre H Meno; April Frazier; Veronique Schulten; Peter S Andersen; Bjoern Peters; Alessandro Sette Journal: Clin Exp Allergy Date: 2016-11-07 Impact factor: 5.018