Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects

Abstract

We tested peptide immunotherapy in cat-allergic humans, using a formation of two synthetic peptides, IPC-1 and IPC-2, each of which is 27 amino acids long and contains T cell-reactive regions of Fel d 1, the major cat allergen. In this exploratory, randomized, double-blind, parallel-group study, 42 subjects received s.c. injections of treatment peptides 250 micrograms or placebo weekly for four consecutive weeks. Changes in immediate- and late-phase skin test reactivity, and in antigen-driven cytokine synthesis were assessed. Epicutaneous (end-point titration) and intradermal tests were performed with cat extract (ALK SQ Cat Hair) containing Fel d 1, before the first injection, then 2, 6 and 24 weeks after the fourth and last injection of peptides or placebo. IL-4, IL-10 and IFN-gamma expression by circulating peripheral blood mononuclear cells (PBMC) in response to cat extract was measured using short-term bulk culture of PBMC and short-term limiting dilution analysis. Subjects who received peptide immunotherapy did not tolerate significantly more cat extract containing Fel d 1 in the skin tests 2, 6 or 24 weeks after the last injection than they did at baseline, and their late-phase responses did not decrease significantly compared to baseline. Substantial IL-4, IL-10 and IFN-gamma responses were observed following primary culture of cat antigen-stimulated PBMC; however, the intensity of cytokine synthesis and the IFN-gamma: IL-4 ratio were unchanged in peptide- and placebo-treated groups 6 and 24 weeks after the last injection. A few hours after the injections, subjects receiving peptides reported more allergic rhinitis and asthma symptoms and more pruritus than those receiving placebo. We conclude that under the conditions tested, peptide immunotherapy did not reduce immediate- or late-phase skin reactivity to cat extract containing Fel d 1 or modify cat antigen-specific cytokine production significantly.

Treatment of established asthma in a murine model using CpG oligodeoxynucleotides

“…One reason for this decline has been the concern for the serious, potentially fatal, adverse effects, most notably anaphylaxis, that have been reported (17) to occur most commonly in asthmatic patients (17,28,41). The introduction of epitope-specific peptide immunotherapy (23,24) has led to the promise of improved safety, with the elimination of epitopes that cause systemic responses, but the efficacy of these agents has been questioned (34).…”

Recombinant Allergens with Reduced Allergenicity but Retaining Immunogenicity of the Natural Allergens: Hybrids of Yellow Jacket and Paper Wasp Venom Allergen Antigen 5s

“…This is in contrast to the allergens modified by the other procedures described in the introduction to this paper, as most known modified allergens lack part or all of their discontinuous B cell epitopes. It is known from studies in animals or humans that denatured allergens (4,34) or T cell epitope peptides of allergens (35)(36)(37)(38) did not induce allergen-specific Ab responses, although they did stimulate allergen-specific T cell responses. Thus, the hybrids may represent a better way to prepare modified allergens for use as vaccines, because they can induce both cellular and Ab responses.…”

Developments in allergen‐specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen‐specific immunoglobulin E and T cell reactivity

“…On the other hand, it was expected that the administration of T cell epitope-derived peptides would induce immune tolerance against the allergen. In the beginning of the 1990s, clinical trials evaluating the concept of SIT with allergen-derived peptides targeting T cells for treating cat allergy were initiated [88][89][90][91]. Since then, the application of allergen-derived peptides containing T cell epitopes has been tested in several clinical studies and indeed no immediate type symptoms were elicited.…”

“…Since then, the application of allergen-derived peptides containing T cell epitopes has been tested in several clinical studies and indeed no immediate type symptoms were elicited. However, treatment with peptides of the major cat allergen, Fel d 1, was still associated with adverse events, primarily the late-onset symptoms of rhinitis, asthma and pruritus [88][89][90][91]. The incidence of late adverse events was related to both peptide dose and the severity of disease [9,92,93].…”