title: Allergen-specific T-cell tolerance induction with allergen-derived long synthetic peptides: results of a phase I trial.
abstract: BACKGROUND
  There is a need to improve the safety and efficacy of allergen-specific immunotherapy. Long synthetic peptide-based immunotherapy was proven safe, immunogenic, and protective in preclinical trials.
  
  
  OBJECTIVE
  To evaluate the safety and immunogenicity of an allergen-derived long synthetic overlapping peptide (LSP) immunotherapy, we designed a double-blind, placebo-controlled phase I clinical trial in patients hypersensitive to bee venom.
  
  
  METHODS
  Patients from the active group were injected at day 0 with a mixture of 3 LSPs mapping the entire PLA2 molecule, a major bee venom allergen, in a dose-escalating protocol to a maintenance dose of 100 microg per peptide repeated at days 4, 7, 14, 42, and 70. The control group was injected with human albumin.
  
  
  RESULTS
  Whereas specific T-cell proliferation in the peptide group increased up to day 14, a sharp decline was observed thereafter, ending in specific T-cell hyporesponsiveness at day 80. Serum-specific IgG4 response was enhanced, in contrast to anti-PLA2 IgE. Specific T-cell cytokine modulation was marked by increased IL-10 and IFN-gamma secretion. LSP injections were well tolerated in all patients except for mild, late allergic reactions in 2 patients at day 70.
  
  
  CONCLUSIONS
  The results of this short-term study demonstrate that LSP-based allergen immunotherapy was safe and able to induce T(H)1-type immune deviation, allergen-specific IL-10 production, and T-cell hyporesponsiveness. LSPs, which offer the advantage of covering all possible T-cell epitopes for any HLA genotype, can be considered candidates for a novel and safe approach of specific immunotherapy.
authors.affiliation: Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Fellrath
authors.forename: Alexander
authors.initials: A
authors.lastname: Kettner
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dufour
authors.forename: Christian
authors.initials: C
authors.lastname: Frigerio
authors.forename: Dominique
authors.initials: D
authors.lastname: Schneeberger
authors.forename: Annette
authors.initials: A
authors.lastname: Leimgruber
authors.forename: Gampietro
authors.initials: G
authors.lastname: Corradin
authors.forename: François
authors.initials: F
authors.lastname: Spertini
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D001514:Bee Venoms / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D010741:Phospholipases A / Q000276:immunology*; D054467:Phospholipases A2; D012882:Skin Tests; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000485:Allergens; D001514:Bee Venoms; D016207:Cytokines; D007074:Immunoglobulin G; D010446:Peptide Fragments; D007073:Immunoglobulin E; D010741:Phospholipases A; D054467:Phospholipases A2