Recombinant T‐cell epitope conjugation: A new approach for Dermatophagoides hypoallergen design

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 fo...

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Published in:Clinical and experimental allergy 2023-02, Vol.53 (2), p.198-209
Main Authors: Fernandes, Antônio Márcio Santana, Silva, Eduardo Santos, Silveira, Elisânia Fontes, Belitardo, Emília Maria Medeiros de Andrade, Santiago, Leonardo Freire, Silva, Raphael Chagas, Santos Alves, Vitor, Carneiro, Deise Malta, Ferreira, Fatima, Jacquet, Alain, Pacheco, Luis Gustavo Carvalho, Alcantara‐Neves, Neuza Maria, Pinheiro, Carina Silva
Format: Article
Language:English
Subjects:
Affinity chromatography
Allergens
allergen‐specific immunotherapy
Allergic diseases
Allergies
Animals
Antigens, Dermatophagoides - immunology
Antigens, Dermatophagoides - pharmacology
Antigens, Dermatophagoides - therapeutic use
Arthropod Proteins
Blocking antibodies
Der p 1 antigen
Dermatophagoides pteronyssinus
Epitopes
Epitopes, T-Lymphocyte - chemistry
Epitopes, T-Lymphocyte - therapeutic use
Humans
Hypersensitivity - drug therapy
hypoallergen
Immune response
immunogenicity
Immunoglobulin E
Immunoglobulin G
Immunological tolerance
Immunotherapy
Immunotherapy - methods
Interleukin-10
Interleukin-4
Interleukin-5
Leukocytes (eosinophilic)
Leukocytes, Mononuclear
Lymphocytes T
Mice
Peripheral blood mononuclear cells
Pyroglyphidae
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Splenocytes
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Summary: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 IFN‐γ, as well as lower levels of IL‐4, IL‐5, IL‐13, TNF‐α 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 IFN‐γ 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. The hybrid rDer p 2231 stimulated in PBMCs isolated from atopic patients, higher levels of IL‐ 2, IL‐10, IL‐15 and IFN‐γ, as well as lower levels of IL‐4, IL‐5, IL‐13, TNF‐α 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, which blocked the IgE binding to the parental allergens in serum of atopic patients. Furthermore, the stimulation of splenocytes from mice treated with rDer p 2231 induced higher levels of IL‐10 and IFN‐γ and decreased the secretion of
ISSN:0954-7894
1365-2222
DOI:10.1111/cea.14238