The hybrid protein BTH2 suppresses allergic airway inflammation in a murine model of HDM‐specific immunotherapy

• Published in: Clinical and experimental allergy 2023-08, Vol.53 (8), p.821-832
• Main Authors: Silva, Eduardo Santos, Santana, Marina Borges Rabelo, Silveira, Elisânia Fontes, Torres, Rogério Tanan, Silva, Raphael Chagas, Fernandes, Antônio Márcio Santana, Belitardo, Emília Maria Medeiros de Andrade, Garcés, Luis Fabián Salazar, Santiago, Leonardo Freire, Urrego, Juan Ricardo, Vilas‐Bôas, Deise Souza, Freitas, Luiz Antônio Rodrigues, Zakzuk, Josefina, Pacheco, Luis Gustavo Carvalho, Cruz, Álvaro Augusto, Ferreira, Fatima, Cooper, Philip, Caraballo, Luis, Pinheiro, Carina da Silva, Alcantara‐Neves, Neuza Maria
• Format: Article
• Language: English
• Subjects: allergen immunotherapy; Allergens; Allergies; Animal models; Asthma; Blo t 5 antigen; Blocking antibodies; Blomia tropicalis; Cytokines; Enzyme-linked immunosorbent assay; experimental model; Goblet cells; Immunoglobulin E; Immunoglobulin G; Immunological tolerance; Immunoregulation; Immunotherapy; Inflammation; Leukocytes (eosinophilic); Lymphocytes T; peripheral blood mononuclear cell; Recombinants; Respiratory tract diseases; vaccine candidate
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/cea.14293

Background 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. Methods 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. Results 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. Conclusions 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.