Therapeutic potential of a novel hybrid protein: Mitigating allergy and airway remodeling in chronic asthma models induced by Dermatophagoides pteronyssinus

Abstract

Background: The house-dust mite Dermatophagoides pteronyssinus is a key trigger of allergic asthma. Therefore, it is essential to develop new vaccines that can alter inflammatory processes and airway remodeling. The goal of this study was to test the hypoallergenic and immunogenic characteristics of the hypoallergen rDer p 2231 in a murine model of chronic asthma induced by D. pteronyssinus.

Methods: For this, we measured the levels of IgE, IgG1, IgG2a, and cytokines produced by mice receiving the rDer p 2231 protein. Histopathological parameters of the chronic inflammatory response were also investigated by assessing inflammation and airway remodeling.

Results: rDer p 2231 given as a therapeutic vaccine, led to a reduction in the production of IgE, eosinophils, and neutrophils, a lower activity of eosinophilic peroxidase in the airways, and an increase in the production of IgG1 and IgG2a antibodies. IgG antibodies blocked IgE binding to parental allergens in sera from atopic patients. Splenocytes, BALF, and lung from mice treated with rDer p 2231 secreted higher levels of Th1 and regulatory cytokines, as well as reduced levels of Th2 cytokines. Histopathological investigation of the lower airways demonstrated reductions in the thickness of the bronchiolar smooth muscle layer, in the subepithelial fibrosis, and in the goblet cells hyperplasia.

Conclusions: Our preclinical studies suggest that rDer p 2231 is a promising candidate for the treatment of D. pteronyssinus allergy, as the hypoallergen has demonstrated the ability to reduce IgE production, induce specific blocking antibodies, restore and balance Th1/Th2 immune responses, and significantly reduce airway remodeling factors. However, additional clinical studies are needed to more accurately assess the efficacy and safety of rDer p 2231 as a vaccine against D. pteronyssinus-induced allergy.

Keywords: Airway remodeling; Allergen-specific immunotherapy; Asthma; Dermatophagoides pteronyssinus; Hypoallergen; Immunogenicity.