Treatment of cat allergy with T-cell reactive peptides.

Abstract

We induced in allergic humans the counterpart of murine experimental T-cell tolerance. T-cell lines from cat-allergic humans were used to map T-cell epitopes for the principal allergen of cat dander, Fel d 1. Two peptides of 27 amino acids each were synthesized to contain the dominant epitopes (ALLERVAX CAT). After a safety trial, we carried out a blinded study of the dose required for efficacy. We randomly divided 95 cat-sensitive patients into placebo, 7.5 micrograms, 75 micrograms, and 750 micrograms groups. Patients received a subcutaneous injection weekly for 4 wk. Before and after treatment, patients were exposed in a room inhabited by live cats and scored by nose and lung symptoms. Baseline nasal and lung scores (+/-SEM) were 6.2 +/- 0.56 and 5.4 +/- 0.73 in the 750 micrograms group; 7.8 +/- 0.53 and 4.7 +/- 0.68 in the placebo group. Six weeks after treatment, scores adjusted for baseline differences were reduced in the 750 micrograms group: -2.3 +/- 4.9 and -2.3 +/- 0.59 compared with -0.84 +/- 0.50 and -0.85 +/- 0.62 in the placebo group. The 75 micrograms group showed intermediate effects and the 7.5 micrograms group no effect. Linear trend analysis indicated a significant dose response effect: p = 0.05 for nose and 0.03 for lung symptoms. Allergic side effects occurred an hour or more after the first 750 micrograms dose in 16 of 24 patients but required little or no treatment with one exception. T-cell reactive treatment peptides safely improved allergic responses to cats.

Inducing Tolerance by Intranasal Administration of Long Peptides in Naive and Primed CBA/J Mice

“…Allergen-derived peptides or adapted approaches (LPs, mutated allergens, allergen fragments, etc.) may be of the utmost interest for the therapy of allergic diseases, since peptides with low or absent IgE-binding capacity, but conserved recognition by T cells, can be easily synthesized, and offer a safe alternative to native allergen for specific immunotherapy (14,18,(51)(52)(53).…”

The Efficacy of Immunotherapy in an Experimental Murine Model of Allergic Asthma Is Related to the Strength and Site of T Cell Activation During Immunotherapy

“…To circumvent the risk of cross-linking of allergen-specific IgE, the use of synthetic peptides containing immunodominant epitopes of allergens has been exploited. In several clinical trials, however, it has been shown that, although some patients showed a reduction of airway symptoms and Th2-associated responses, Fel d I peptide immunotherapy elicited allergic symptoms and late asthmatic reactions in cat-allergic asthmatics (7,8). Moreover, we recently showed that in OVA-sensitized mice, s.c. immunotherapy with the immunodominant T cell epitope OVA 323-339 enhanced both airway hyperresponsiveness (AHR) 3 and eosinophilia upon OVA challenge (9), while an in vitro defined superagonistic analogue of this OVA 323-339 epitope had a beneficial effect (10).…”

Formation of Disulfide Bonds and Homodimers of the Major Cat Allergen Fel d 1 Equivalent to the Natural Allergen by Expression in Escherichia coli

“…The amino acid sequence (17) and the disulfide bonds as determined by nano-ESI mass spectrometry after tryptic digestion of the E. coli expressed (His) 6 -tagged rFel d 1(2 ϩ 1) fusion protein is shown in Fig. 1.…”

“…Treatment of cat allergy by allergen injections is often employed, but clinical results are, in part, controversial. Because only crude dander extract is available for the treatment of cat allergy (4,5), alternative formulations have been proposed (6,7).…”