Introduction Allergen‐specific immunotherapy (AIT) represents a curative approach for treating allergies. In the tropical and subtropical regions of the world, Blomia tropicalis (Blo t 5 and Blo t 21) is the likely dominant source of indoor allergens. Aim To generate a hypoallergenic Blo t 5/Blo t 21 hybrid molecule that can treat allergies caused by B tropicalis . Methods Using in silico design of B tropicalis hybrid proteins, we chose two hybrid proteins for heterologous expression. Wild‐type Blo t 5/Blo t 21 hybrid molecule and a hypoallergenic version, termed BTH1 and BTH2, respectively, were purified by ion exchange and size exclusion chromatography and characterized by physicochemical, as well as in vitro and in vivo immunological, experiments. Results BTH1, BTH2 and the parental allergens were purified to homogeneity and characterized in detail. BTH2 displayed the lowest IgE reactivity that induced basophil degranulation using sera from allergic rhinitis and asthmatic patients. BTH2 essentially presented the same endolysosomal degradation pattern as the shortened rBlo t 5 and showed a higher resistance towards degradation than the full‐length Blo t 5. In vivo immunization of mice with BTH2 led to the production of IgG antibodies that competed with human IgE for allergen binding. Stimulation of splenocytes from BTH2‐immunized mice produced higher levels of IL‐10 and decreased secretion of IL‐4 and IL‐5. In addition, BTH2 stimulated T‐cell proliferation in PBMCs isolated from allergic patients, with secretion of higher levels of IL‐10 and lower levels of IL‐5 and IL‐13, when compared to parental allergens. Conclusions and Clinical Relevance BTH2 is a promising hybrid vaccine candidate for immunotherapy of Blomia allergy. However, further pre‐clinical studies addressing its efficacy and safety are needed.

LETTERS TO THE EDITOR in infrequent phenotypes such as isolated angioedema by SRs and multiple SRs, which may be misdiagnosed as CRs. This procedure is useful not only for reducing the number of patients who are unnecessarily avoiding NSAIDs but also for extending their therapeutic possibilities. Although such accurate diagnosis requires facilities and trained personal in this field, it will improve the allergological workup and, consequently, patients' management.

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Background: Allergen-specific immunotherapy (AIT) is the only clinical approach that can potentially cure some allergic diseases by inducing immunological tolerance.Dermatophagoides pteronyssinus is considered as the most important source of mite allergens worldwide, with high sensitization rates for the major allergens Der p 1, Der p 2 and Der p 23. The aim of this work is to generate a hypoallergenic hybrid molecule containing T-cell epitopes from these three major allergens. Methods: The hybrid protein termed Der p 2231 containing T-cell epitopes was purified by affinity chromatography. The human IgE reactivity was verified by comparing those with the parental allergens. The hybrid was also characterized immunologically through an in vivo mice model. Results: The hybrid rDer p 2231 stimulated in peripheral blood mononuclear cells (PBMCs) isolated from allergic patients with higher levels of IL-2, IL-10, IL-15 and IFNγ, as well as lower levels of IL-4, IL-5, IL-13, TNFα and GM-CSF. The use of hybrid molecules as a therapeutic model in D. pteronyssinus allergic mice led to the reduction of IgE production and lower eosinophilic peroxidase activity in the airways. We found increased levels of IgG antibodies that blocked the IgE binding to the parental allergens in the serum of allergic patients. Furthermore, the stimulation of splenocytes from mice treated with rDer p 2231 induced higher levels of IL-10 and IFNγ and decreased the secretion of IL-4 and IL-5, when compared with parental allergens and D. pteronyssinus extract. Conclusions: rDer p 2231 has the potential to be used in AIT in patients co-sensitized with D. pteronyssinus major allergens, once it was able to reduce IgE production, inducing allergen-specific blocking antibodies, restoring and balancing Th1/Th2 immune responses, and inducing regulatory T-cells.

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