Fel d 1-derived synthetic peptide immuno-regulatory epitopes show a long-term treatment effect in cat allergic subjects

Clin Exp Allergy. 2015 May;45(5):974-981. doi: 10.1111/cea.12488.

Abstract

Background: Cat-PAD, the first in a new class of synthetic peptide immuno-regulatory epitopes (SPIREs), was shown to significantly improve rhinoconjunctivitis symptoms in subjects with cat allergy up to 1 year after the start of a short course of treatment.

Objective: To evaluate the long-term effects of Cat-PAD on rhinoconjunctivitis symptoms following standardized allergen challenge 2 years after treatment.

Methods: In a randomized, double-blind, placebo-controlled, parallel group study, subjects were exposed to cat allergen in an environmental exposure chamber (EEC) before and after treatment with two regimens of Cat-PAD (either eight doses of 3 nmol or four doses of 6 nmol) given intradermally over a 3-month period. In this follow-up study, changes from baseline in rhinoconjunctivitis symptoms were reassessed 2 years after the start of treatment.

Results: The primary endpoint showed a mean reduction in total rhinoconjunctivitis symptom scores of 3.85 units in the 4 × 6 nmol Cat-PAD group compared to placebo 2 years after the start of treatment (P = 0.13), and this difference was statistically significant in the secondary endpoint at the end of day 4 when the cumulative allergen challenge was greatest (P = 0.02). Consistent reductions in nasal symptoms of between 2 and 3 units were observed for 4 × 6 nmol Cat-PAD compared to placebo between the 2 and 3 h time points on days 1-4 of EEC challenge at 2 years (P < 0.05). The 8 × 3 nmol dose did not show a meaningful effect in this study.

Conclusion and clinical relevance: A persistent, clinically meaningful reduction in rhinoconjunctivitis symptoms was observed on EEC challenge 2 years after the start of a short course of treatment with 4 × 6 nmol Cat-PAD. This study is the first to provide evidence of a long-term therapeutic effect with this new class of SPIREs.

Keywords: Fel d 1; SPIREs; T-cell epitopes; allergic rhinitis; allergic rhinoconjunctivitis; cat allergy; immune tolerance; immunotherapy; persistence.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allergens / administration & dosage
  • Allergens / immunology
  • Animals
  • Cats
  • Conjunctivitis, Allergic / diagnosis
  • Conjunctivitis, Allergic / drug therapy
  • Conjunctivitis, Allergic / immunology
  • Desensitization, Immunologic* / adverse effects
  • Epitopes / administration & dosage*
  • Epitopes / immunology*
  • Female
  • Follow-Up Studies
  • Glycoproteins / chemistry
  • Glycoproteins / immunology*
  • Humans
  • Hypersensitivity / diagnosis
  • Hypersensitivity / immunology*
  • Hypersensitivity / therapy*
  • Male
  • Middle Aged
  • Peptides / administration & dosage*
  • Peptides / chemical synthesis
  • Peptides / immunology*
  • Rhinitis, Allergic / diagnosis
  • Rhinitis, Allergic / drug therapy
  • Rhinitis, Allergic / immunology
  • Treatment Outcome
  • Young Adult

Substances

  • Allergens
  • Epitopes
  • Glycoproteins
  • Peptides
  • Fel d 1 protein, Felis domesticus