Dados do Trabalho


Título

BTH2 allergy vaccine reduces allergic inflammation in a murine model of asthma induced by Blomia tropicalis

Resumo

Introduction: Blomia tropicalis is an important allergen source. It can be responsible for both, sensitization and allergenic symptoms of allergic rhinitis and allergic asthma patients. As an option for treatment, allergen-specific immunotherapy can be used to induce a tolerogenic immunological response, with consequent improvement of symptoms. Our goal in this study was to test the therapeutic potential of a recombinant hypoallergenic protein, termed BTH2, in a murine model of asthma induced by B. tropicalis. Methods: BTH2 was tested in a chronic allergy model induced by B. tropicalis mite soluble extract. This extract was used to sensitize and challenge male A/J mice in two groups. One group was treated with the hypoallergenic protein, in a protocol lasting a total of 4 months. After euthanizing the animals, several safety, toxicity, and immunological efficacy parameters were evaluated by various in vitro assays. Results: Treatment with BTH2 was not hepatotoxic and reduced the total number of cells in the bronchoalveolar lavage fluid, highlighting the significant reduction of eosinophils and their peroxidase activity. There was also a reduction in serological specific IgE against the mite extract and rBlo t 5 and rBlo t 21 upon treatment with BTH2. In contrast, hypoallergen’s treatment increased serological specific IgG antibodies, which inhibited IgE-binding capacity of human reactive sera. There was also an increased production of specific IgA antibodies in sera and in the lungs of treated mice. Down-regulation of TH2 cytokines was observed in treated mice in both, the lungs and in splenocytes culture. However, the most significant reduction was in IL-1β levels. Conversely, IL-10 and TGF-β1 were up-regulated in treated animals. Conclusions: BTH2 was further confirmed as an allergy vaccine, displaying appealing safety and efficacy features. Therefore, the hypoallergen may be used in future clinical trials with B. tropicalis allergic patients.

Área

Imunoterapia e imunobiológicos

Autores

Eduardo Santos da Silva, Jennifer Emily Anunciação Sousa, Lorena Miranda de Souza, Raphael Chagas da Silva, Carolina Orrico Melo Ferreira de Jesus, Antônio Márcio Santana Fernandes, Vitor Lima Miranda Melo, Neuza Maria Alcantara-Neves, Carina da Silva Pinheiro, Luis Gustavo Carvalho Pacheco