title: Carrier-bound nonallergenic Der p 2 peptides induce IgG antibodies blocking allergen-induced basophil activation in allergic patients.
abstract: 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.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: K-W
authors.initials: KW
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Focke-Tejkl
authors.forename: K
authors.initials: K
authors.lastname: Blatt
authors.forename: M
authors.initials: M
authors.lastname: Kneidinger
authors.forename: A
authors.initials: A
authors.lastname: Gieras
authors.forename: F
authors.initials: F
authors.lastname: Dall'Antonia
authors.forename: I
authors.initials: I
authors.lastname: Faé
authors.forename: G
authors.initials: G
authors.lastname: Fischer
authors.forename: W
authors.initials: W
authors.lastname: Keller
authors.forename: P
authors.initials: P
authors.lastname: Valent
authors.forename: R
authors.initials: R
authors.lastname: Valenta
authors.forename: S
authors.initials: S
authors.lastname: Vrtala
mesh_terms: D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D039741:Antigens, Dermatophagoides / Q000737:chemistry / Q000276:immunology*; D060829:Arthropod Proteins / Q000737:chemistry / Q000276:immunology*; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D006433:Hemocyanins / Q000737:chemistry; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D039981:Pyroglyphidae / Q000276:immunology; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000485:Allergens; D019138:Antibodies, Blocking; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; C451163:Dermatophagoides pteronyssinus antigen p 2; C427944:ENPP3 protein, human; D007074:Immunoglobulin G; D010455:Peptides; D018074:Vaccines, Conjugate; D007073:Immunoglobulin E; D006433:Hemocyanins; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; C032808:keyhole-limpet hemocyanin