RESUMO
BACKGROUND: Allergic rhinoconjunctivitis is an increasingly common source of morbidity, with sensitivity to cats accounting for 10% to 15% of disease burden. Allergy to cats is also a major risk factor for the development of asthma. OBJECTIVES: We sought to probe the persistence of the treatment effect of a novel F el d 1-derived peptide antigen desensitization (Cat-PAD) 1 year after the start of treatment in subjects with cat allergy-induced rhinoconjunctivitis after standardized allergen challenge. METHODS: In a randomized, double-blind, placebo-controlled, parallel-group clinical trial, subjects attended an environmental exposure chamber in which they were exposed to cat allergen before and after treatment with 2 different regimens of Cat-PAD over a 3-month period. Clinical efficacy was assessed as a change in total rhinoconjunctivitis symptom scores 18 to 22 weeks and 50 to 54 weeks after the start of treatment. RESULTS: Treatment with Cat-PAD showed greater efficacy with 4 administrations of a 6-nmol dose 4 weeks apart than with 8 administrations of a 3-nmol dose 2 weeks apart. The treatment effect of 6 nmol persisted 1 year after the start of treatment and was significantly different from that of 3 nmol (P = .0342) and placebo (P = .0104). The treatment effect was apparent on both nasal and ocular symptoms at 1 year. CONCLUSIONS: A short course of Cat-PAD improves the ocular and nasal components of rhinoconjunctivitis symptoms in subjects with cat allergy, with the treatment effect persisting 1 year after the start of treatment.
Assuntos
Alérgenos/imunologia , Conjuntivite Alérgica/terapia , Dessensibilização Imunológica , Glicoproteínas/imunologia , Peptídeos/imunologia , Adolescente , Adulto , Idoso , Alérgenos/administração & dosagem , Alérgenos/química , Sequência de Aminoácidos , Animais , Gatos , Conjuntivite Alérgica/imunologia , Dessensibilização Imunológica/efeitos adversos , Feminino , Glicoproteínas/química , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Peptídeos/administração & dosagem , Peptídeos/química , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Allergic sensitization to cat allergens is common and represents a major risk factor for asthma. Specific immunotherapy (SIT) is effective but cumbersome and associated with IgE-dependent adverse events. Immunotherapy targeting allergen-specific T cells, with synthetic peptides representing T-cell epitopes, might improve safety and reduce the duration of treatment. OBJECTIVE: We sought to define major T-cell epitopes of Fel d 1 for peptide immunotherapy, generate a peptide vaccine, and evaluate its safety and tolerability in subjects with cat allergy. METHODS: We determined the binding affinities of Fel d 1 peptides for 10 commonly expressed HLA-DR molecules. Functionally immunodominant peptides were identified by means of proliferation and cytokine secretion. Histamine-releasing activity was assessed, and a peptide vaccine was formulated. Safety and tolerability were evaluated in a dose-ranging phase IIa clinical trial. RESULTS: MHC-binding sequences were identified throughout Fel d 1. Some regions contained multiple overlapping T-cell epitopes that bound multiple MHC molecules. Immunodominant sequences were identified on the basis of proliferative and cytokine (IFN-γ, IL-10, and IL-13) responses. Cat allergen extract, but not peptides, induced histamine release in blood basophils. A single administration of peptide vaccine was safe and well tolerated. The dose of vaccine resulting in the greatest inhibition of the late-phase skin response to intradermal whole allergen challenge was 3 nmol. CONCLUSIONS: Fel d 1 contains multiple overlapping MHC-binding motifs. A peptide vaccine comprising the immunodominant regions of the allergen was safe and well tolerated when given to subjects with cat allergy as a single dose. The dose of vaccine resulting in the greatest reduction in late-phase skin response was defined for future clinical development.