Allergen-specific T-cell tolerance induction with allergen-derived long synthetic peptides: results of a phase I trial

J Allergy Clin Immunol. 2003 Apr;111(4):854-61. doi: 10.1067/mai.2003.1337.


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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / immunology*
  • Bee Venoms / immunology*
  • Cytokines / biosynthesis
  • Double-Blind Method
  • Female
  • Humans
  • Immune Tolerance*
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Immunoglobulin G / classification
  • Immunotherapy
  • Male
  • Middle Aged
  • Peptide Fragments / immunology*
  • Phospholipases A / immunology*
  • Phospholipases A2
  • Skin Tests
  • T-Lymphocytes / immunology*


  • Allergens
  • Bee Venoms
  • Cytokines
  • Immunoglobulin G
  • Peptide Fragments
  • Immunoglobulin E
  • Phospholipases A
  • Phospholipases A2