Basic and Clinical Immunology
Allergen-specific T-cell tolerance induction with allergen-derived long synthetic peptides: Results of a phase I trial,☆☆

https://doi.org/10.1067/mai.2003.1337Get rights and content

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 μg 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-γ 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 TH1-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. (J Allergy Clin Immunol 2003;111:854-61.)

Section snippets

Methods

Sixteen patients hypersensitive to BV were recruited from the Outpatient Clinic of the Division of Allergy and Immunology, Lausanne, Switzerland (9 men, 7 women). All patients gave informed consent to the study, and study protocols were approved by the Hospital Review Board. Criteria for enrollment were grade I to IV systemic hypersensitivity reaction to honey bee field sting (according to Müller classification14), positive anti-PLA2 and anti-whole BV-specific IgE (>0.35 kU/L as titrated by CAP

Patient data

Patients were randomly assigned to the LSP or control (albumin) groups. In the LSP group, the mean age of patients was 39 ± 14 years (5 men, 4 women). One patient had a history of grade I hypersensitivity to BV, 7 had grade III, and 1 had grade IV, according to Müller classification. EPC for ID tests to BV was 10−1.7 μg/mL (geometric mean). Mean serum anti-BV-specific IgE level was 21.5 ± 33.9 kU/L. In the control group, the mean age was 40 ± 10 years (4 men, 3 women). One patient previously

Discussion

We have shown in this study that a peptide-based allergen immunotherapy with LSPs derived from PLA2, a major BV allergen, was able to induce T-cell anergy, immune deviation toward a TH1-type T-cell cytokine response, enhanced IL-10 secretion, and PLA2-specific IgG4 production. LSP immunotherapy was safe and did not induce severe systemic reactions, though dose cumulation appeared to induce mild, nonimmediate reactions in two patients.

The fact that LSPs could be injected without any local or

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    Supported by the CHUV/UNIL/EPFL Common Program in Medical Engineering and by the Swiss National Fund for Scientific Research no. 3100-059482.

    ☆☆

    Reprint requests: Dr F. Spertini, Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon, Lausanne 1011, Switzerland.

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