DESENVOLVIMENTO DE UM HIPOALÉRGENO MULTICOMPONENTE DE EPÍTOPOS DE CÉLULAS T DOS ALERGENOS Der p 1, Der p 2 e Der p 23 E SEU USO POTENCIAL NO TRATAMENTO DA ALERGIA AO ÁCARO Dermatophagoides pteronyssinu

Abstract

Introduction: Exposure to house dust mites, such as Dermatophagoides pteronyssinus, triggers reactions that stimulate and induce the pathophysiology of allergic diseases, such as asthma. Allergen-specific immunotherapy (AIT) is the only treatment capable of inducing tolerance to allergens and the only alternative to current pharmacological treatment, which has adverse effects. Although some AIT protocols are performed using crude extracts, bringing some limitations, new approaches such as the hybrid hypoallergens of T cell epitopes brought innovation in the area. These constructs increase immunogenicity and improve production scale, since only one vaccine formulation will be need. Objective: To produce a hypoallergenic hybrid protein based on T-cells epitopes of the main allergens of the dust mite Dermatophagoides pteronyssinus for use in immunotherapy in allergic diseases caused by this mite. Methods: The rDer p 2231 hybrid hypoallergen, engineered using T cell epitopes from Der p 1, Der p 2 and Der p 23 allergens and purified by affinity chromatography, had its reactivity to human IgE verified in comparison to parental allergens. A total of 18 cytokines were evaluated in the supernatant of PBMCs from atopic and non-atopic individuals, stimulated with rDer p 2231. The therapeutic potential of the hybrid rDer p 2231 was also evaluated through acute and chronic murine models of D. pteronyssinus mite allergy. Results: PBMCs isolated from atopic patients and splenocytes from mice, when stimulated with rDer p 2231, produced higher levels of Th1 profile cytokines and regulatory cytokines, while reducing Th2 cytokines. The use of rDer p 2231 as a therapeutic vaccine led to reduced IgE production and lower eosinophilic peroxidase activity in the airways of mice allergic to D. pteronyssinus. The hypoallergen also acted therapeutically in the chronic model of allergy, significantly reducing smooth muscle hypertrophy, decreased subbasal membrane fibrosis, goblet cell hyperplasia and allergic inflammatory response. Conclusion: rDer p 2231 is a multicomponent hybrid molecule with potential to be used in AIT in patients co-sensitized to major D. pteronyssinus allergens, since it was able to reduce IgE production, inducing allergen-specific blocking antibodies, restoring and balancing Th1/Th2 responses and leading to the induction of regulatory T cells, in addition to reducing the tissue pathological effects associated with chronic asthma.