免疫疗法
免疫学
过敏性炎症
炎症
医学
化学
免疫系统
作者
Eduardo Santos da Silva,Marina Borges Rabêlo de Santana,Elisânia Fontes Silveira,Rogério Tanan Torres,Raphael Chagas Silva,Antônio Márcio Santana Fernandes,Emília Maria Medeiros de Andrade Belitardo,Luís Fabián Salazar Garcés,Leonardo Freire Santiago,Juan Ricardo Urrego,Deise Souza Vilas-Bôas,Luiz Antônio Rodrigues de Freitas,Josefina Zakzuk,Luis Gustavo Carvalho Pacheco,Álvaro Augusto Cruz,Fátima Ferreira,Philip J. Cooper,Luis Caraballo,Carina S. Pinheiro,Neuza Maria Alcantara-Neves
摘要
Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment approach to change disease-causing allergens. Hypoallergenic derivatives show promise as potential therapeutics, amongst which BTH2 was designed to induce tolerance against Blomia tropicalis allergy. Our aim was to investigate the hypoallergenicity and immunoregulatory activity of BTH2 in vitro and its therapeutic potential in a mouse model of AIT.Recombinant Blo t 5 and Blo t 21 allergens and their hybrid derivatives (BTH1 and BTH2) were expressed and purified. IgE binding capacity was tested by ELISA using sera from Brazilian, Colombian, and Ecuadorian subjects. Secretion of cytokines in supernatants from human cell cultures was measured following stimulation with the four recombinants and controls. The capacity of BTH2 to ameliorate allergic airway inflammation induced by B. tropicalis extract was evaluated in a murine model of AIT.rBlo t 5 and rBlo t 21 were identified as major allergens in Latin American patients, and BTH2 had the lowest IgE binding. In vitro stimulation of human cells induced greater levels of IL-10 and IFN-γ and reduced the secretion of Th2 cytokines. BTH2 ameliorated allergic airway inflammation in B. tropicalis-challenged A/J mice, as evidenced by the histopathological and humoral biomarkers: decreased Th2 cytokines and cellular infiltration (especially eosinophils), lower activity of eosinophil peroxidase, an increase in IgG blocking antibodies and strong reduction of mucus production by goblet cells.Our study shows that BTH2 represents a promising candidate for the treatment of B. tropicalis allergy with hypoallergenic, immune regulatory and therapeutic properties. Further pre-clinical studies are required in murine models of chronic asthma to further address the efficacy and safety of BTH2 as a vaccine against B. tropicalis-induced allergy.
科研通智能强力驱动
Strongly Powered by AbleSci AI