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

Abstract

BackgroundAllergen‐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.MethodsRecombinant 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.ResultsrBlo 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.ConclusionsOur 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.

Immunotherapy and prevention of allergic diseases

“…In this month's issue, we include three exciting editor's choice studies. The first, by da Silva et al, 1 discusses how hypoallergenic derivatives of Blo t21, a storage and house dust mite, may possess immunomodulatory properties and may serve as a candidate for a safer allergen immunotherapy. Conventional allergen immunotherapy using crude allergen extracts can be effective in treating allergies, 2,3 however, there are also some challenges.…”

“…The first, by da Silva et al, 1 discusses how hypoallergenic derivatives of Blo t21, a storage and house dust mite, may possess immunomodulatory properties and may serve as a candidate for a safer allergen immunotherapy. Conventional allergen immunotherapy using crude allergen extracts can be effective in treating allergies, 2,3 In an open follow-up 2 years after treatment, symptoms, medication intake and quality of life were significantly improved in the actively treated group.…”

“…Further work is needed to establish whether there is a link between these changes in the infant gut microbiome and allergic disorders (Figure 2). Mohamed H. Shamji 1,2 Robert J. Boyle…”