دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: The hybrid protein BTH2 suppresses allergic airway inflammation in a murine model of HDM-specific immunotherapy.
المؤلفون: da Silva ES; Laboratory of Allergology and Acarology (LAA), Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.; Post-Graduate Program in Biotechnology of the Northeast Biotechnology Network (RENORBIO), Maceió, Brazil., de Santana MBR; Laboratory of Allergology and Acarology (LAA), Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.; Post-Graduate Program in Immunology, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., Silveira EF; Laboratory of Allergology and Acarology (LAA), Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., Torres RT; Laboratory of Allergology and Acarology (LAA), Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., Silva RC; Laboratory of Allergology and Acarology (LAA), Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.; Post-Graduate Program in Immunology, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., Fernandes AMS; Laboratory of Allergology and Acarology (LAA), Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., Belitardo EMMA; Laboratory of Allergology and Acarology (LAA), Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.; Post-Graduate Program in Immunology, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FioCruz), Salvador, Brazil., Garcés LFS; Laboratory of Allergology and Acarology (LAA), Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.; Post-Graduate Program in Immunology, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.; Faculty of Health Sciences, Technical University of Ambato, Ambato, Ecuador., Santiago LF; Laboratory of Allergology and Acarology (LAA), Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., Urrego JR; Department of Pharmacy, University of Cartagena, Cartagena, Colombia., Vilas-Bôas DS; Post-Graduate Program in Immunology, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.; Laboratory of Histotechnology, Department of Biomorphology, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., de Freitas LAR; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FioCruz), Salvador, Brazil.; Department of Pathology of the School of Medicine, Federal University of Bahia, Salvador, Brazil., Zakzuk J; Institute of Immunological Research, University of Cartagena, Cartagena, Colombia., Pacheco LGC; Laboratory of Allergology and Acarology (LAA), Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., Cruz ÁA; ProAR Foundation and Federal University of Bahia, Salvador, Brazil., Ferreira F; Department of Biosciences, Paris-Lodron University of Salzburg, Salzburg, Austria., Cooper P; Institute of Infection and Immunity, St George's University of London, London, UK.; School of Medicine, International University of Ecuador, Quito, Ecuador., Caraballo L; Institute of Immunological Research, University of Cartagena, Cartagena, Colombia., Pinheiro CDS; Laboratory of Allergology and Acarology (LAA), Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.; Post-Graduate Program in Immunology, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil., Alcantara-Neves NM; Laboratory of Allergology and Acarology (LAA), Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.; Post-Graduate Program in Biotechnology of the Northeast Biotechnology Network (RENORBIO), Maceió, Brazil.; Post-Graduate Program in Immunology, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.
المصدر: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Clin Exp Allergy] 2023 Aug; Vol. 53 (8), pp. 821-832. Date of Electronic Publication: 2023 Feb 13.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 8906443 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2222 (Electronic) Linking ISSN: 09547894 NLM ISO Abbreviation: Clin Exp Allergy Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford : Blackwell Scientific Publications, c1989-
مواضيع طبية MeSH: Hypersensitivity*/therapy, Humans ; Mice ; Animals ; Disease Models, Animal ; Allergens ; Inflammation ; Cytokines ; Desensitization, Immunologic ; Immunoglobulin E
مستخلص: 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.
(© 2023 John Wiley & Sons Ltd.)
التعليقات: Comment in: Clin Exp Allergy. 2023 Aug;53(8):788-790. (PMID: 37559562)
References: GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204-1222.
Caraballo L, Zakzuk J, Lee BW, et al. Particularities of allergy in the tropics. World Allergy Organ J. 2016;9:20.
Rodriguez A, Brickley E, Rodrigues L, Normansell RA, Barreto M, Cooper PJ. Urbanisation and asthma in low-income and middle-income countries: a systematic review of the urban-rural differences in asthma prevalence. Thorax. 2019;74(11):1020-1030.
Cooper PJ, Chis Ster I, Chico ME, et al. Impact of early life geohelminths on wheeze, asthma and atopy in Ecuadorian children at 8 years. Allergy. 2021;76(9):2765-2775.
Ye Q, He X-O, D'Urzo A. A review on the safety and efficacy of inhaled corticosteroids in the management of asthma. Pulm Ther. 2017;3(1):1-18.
Silva ES, Pinheiro CS, Quintella CM, Ferreira F, C Pacheco LG, Alcantara-Neves NM. Advances in patent applications related to allergen immunotherapy. Expert Opin Ther Pat. 2016;26(6):657-668.
Dhami S, Kakourou A, Asamoah F, et al. Allergen immunotherapy for allergic asthma: a systematic review and meta-analysis. Allergy. 2017;72(12):1825-1848.
Kucuksezer UC, Ozdemir C, Cevhertas L, Ogulur I, Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy and allergen tolerance. Allergol Int. 2020;69(4):549-560.
Fritzsching B, Contoli M, Porsbjerg C, et al. Long-term real-world effectiveness of allergy immunotherapy in patients with allergic rhinitis and asthma: results from the REACT study, a retrospective cohort study. Lancet Reg Health Eur. 2022;13:100275.
Valenta R, Karaulov A, Niederberger V, et al. Allergen extracts for In vivo diagnosis and treatment of allergy: is there a future? J Allergy Clin Immunol Pract. 2018;6(6):1845-1855.e2.
Hossny E, Ebisawa M, El-Gamal Y, et al. Challenges of managing food allergy in the developing world. World Allergy Organ J. 2019;12(11):100089.
Ferreira F, Wolf M, Wallner M. Molecular approach to allergy diagnosis and therapy. Yonsei Med J. 2014;55(4):839-852.
Huang HJ, Curin M, Banerjee S, et al. A hypoallergenic peptide mix containing T cell epitopes of the clinically relevant house dust mite allergens. Allergy. 2019;74(12):2461-2478.
Yang L, Kulis M. Hypoallergenic proteins for the treatment of food allergy. Curr Allergy Asthma Rep. 2019;19(2):15.
Silva ESD, Pinheiro CS, Pacheco LGC, Alcantara-Neves NM. Dermatophagoides spp. hypoallergens design: what has been achieved so far? Expert Opin Ther Pat. 2020;30(3):163-177.
Miller JD. The role of dust mites in allergy. Clin Rev Allergy Immunol. 2019;57(3):312-329.
Santos da Silva E, Asam C, Lackner P, et al. Allergens of Blomia tropicalis: an overview of recombinant molecules. Int Arch Allergy Immunol. 2017;172(4):203-214.
da Silva ES, Aglas L, Pinheiro CS, et al. A hybrid of two major Blomia tropicalis allergens as an allergy vaccine candidate. Clin Exp Allergy. 2020;50:835-847.
Alcantara-Neves NM, Silva ES, Pacheco LGC, Pinheiro CS, Federal University of Bahia. Design and production of hypoallergenic recombinant hybrid proteins constructed from groups 5 and 21 of Blomia tropicalis for prophylactic use and treatment of allergic diseases. 2018. Brazilian patent, filed in the National Institute of Industrial Property 26 June 2018 and issued 23 March 2021.
Baqueiro T, Russo M, Silva VM, et al. Respiratory allergy to Blomia tropicalis: immune response in four syngeneic mouse strains and assessment of a low allergen-dose, short-term experimental model. Respir Res. 2010;11:51.
Santos da Silva E, Marques Ponte JC, Barbosa da Silva M, et al. Proteomic analysis reveals allergen variability among breeds of the dust mite Blomia tropicalis. Int Arch Allergy Immunol. 2019;180(3):159-172.
da Silva ES, Huber S, Alcantara-Neves NM, et al. N-terminal peptide deletion influences immunological and structural features of Blo t 5. Allergy. 2020;75(6):1503-1507.
Cruz AA, Souza-Machado A, Franco R, et al. The impact of a program for control of asthma in a low-income setting. World Allergy Organ J. 2010;3(4):167-174.
Koshak EA. Classification of asthma according to revised 2006 GINA: evolution from severity to control. Ann Thorac Med. 2007;2(2):45-46.
da Silva ES, Pacheco LGC, Fernandes AMS, et al. Purification and characterisation of the dimeric group 12 allergen from Blomia tropicalis heterologously expressed by Escherichia coli Top10F. Mol Biol Rep. 2021;48(4):3405-3416.
Santos LN, Gallo MB, Silva ES, et al. A proteomic approach to identify proteins from Trichuris trichiura extract with immunomodulatory effects. Parasite Immunol. 2013;35(5-6):188-193.
Amor D, Santos LN, Silva ES, et al. Toxocara canis extract fractions promote mainly the production of Th1 and regulatory cytokines by human leukocytes in vitro. Acta Trop. 2022;234:106579.
Metsalu T, Vilo J. ClustVis: a web tool for visualizing clustering of multivariate data using principal component analysis and heatmap. Nucleic Acids Res. 2015;43(W1):W566-W570.
Santos Serafim Machado M, Ferreira Silva HB, Rios R, et al. The anti-allergic activity of Cymbopogon citratus is mediated via inhibition of nuclear factor kappa B (Nf-Kappab) activation. BMC Complement Altern Med. 2015;15:168.
Tanaka H, Masuda T, Tokuoka S, et al. The effect of allergen-induced airway inflammation on airway remodeling in a murine model of allergic asthma. Inflamm Res. 2001;50(12):616-624.
Leick-Maldonado EA, Kay FU, Leonhardt MC, et al. Comparison of glucocorticoid and cysteinyl leukotriene receptor antagonist treatments in an experimental model of chronic airway inflammation in guinea-pigs. Clin Exp Allergy. 2004;34(1):145-152.
Ahn JH, Kim CH, Kim YH, et al. Inflammatory and remodeling events in asthma with chronic exposure to house dust mites: a murine model. J Korean Med Sci. 2007;22(6):1026-1033.
Cerps S, Sverrild A, Ramu S, et al. House dust mite sensitization and exposure affects bronchial epithelial anti-microbial response to viral stimuli in patients with asthma. Allergy. 2022;77(8):2498-2508.
Costa RS, Carneiro TC, Cerqueira-Lima AT, et al. Ocimum gratissimum Linn. and rosmarinic acid, attenuate eosinophilic airway inflammation in an experimental model of respiratory allergy to Blomia tropicalis. Int Immunopharmacol. 2012;13(1):126-134.
Oliveira TT, Campos KM, Cerqueira-Lima AT, et al. Potential therapeutic effect of Allium cepa L. and quercetin in a murine model of Blomia tropicalis induced asthma. Daru. 2015;23:18.
Pinheiro CS, Silva ES, de Andrade Belitardo EMM, et al. En route to personalized medicine: uncovering distinct IgE reactivity pattern to house dust mite components in Brazilian and Austrian allergic patients. Clin Transl Allergy. 2021;11(1):e12004.
Zakzuk J, Acevedo N, Cifuentes L, et al. Early life IgE responses in children living in the tropics: a prospective analysis. Pediatr Allergy Immunol. 2013;24(8):788-797.
Virchow JC, Backer V, Kuna P, et al. Efficacy of a house dust mite sublingual allergen immunotherapy tablet in adults with allergic asthma: a randomized clinical trial. JAMA. 2016;315(16):1715-1725.
Boonpiyathad T, Satitsuksanoa P, Akdis M, Akdis CA. Il-10 producing T and B cells in allergy. Semin Immunol. 2019;44:101326.
Rauber MM, Mobs C, Campana R, et al. Allergen immunotherapy with the hypoallergenic B-cell epitope-based vaccine BM32 modifies IL-10- and IL-5-secreting T cells. Allergy. 2020;75(2):450-453.
Schulke S. Induction of interleukin-10 producing dendritic cells as a tool to suppress allergen-specific T helper 2 responses. Front Immunol. 2018;9:455.
Fernandez-Santamaria R, Satitsuksanoa P. Engineered IL-10: a matter of affinity. Allergy. 2022;77(3):1067-1069.
Martinez D, Munera M, Cantillo JF, et al. An engineered hybrid protein from Dermatophagoides pteronyssinus allergens shows hypoallergenicity. Int J Mol Sci. 2019;20(12):3025.
Hofer H, Asam C, Hauser M, et al. Tackling Bet v 1 and associated food allergies with a single hybrid protein. J Allergy Clin Immunol. 2017;140(2):525-533.e10.
Wallner M, Hauser M, Himly M, et al. Reshaping the Bet v 1 fold modulates T(H) polarization. J Allergy Clin Immunol. 2011;127(6):1571-1578.e9.
Zhao BB, Diao JD, Liu ZM, Li CP, Jiang YX. Generation of a chimeric dust mite hypoallergen using DNA shuffling for application in allergen-specific immunotherapy. Int J Clin Exp Pathol. 2014;7(7):3608-3619.
Pichler U, Asam C, Weiss R, et al. The fold variant BM4 is beneficial in a therapeutic Bet v 1 mouse model. Biomed Res Int. 2013;2013:832404.
Sancho AI, Wallner M, Hauser M, et al. T cell epitope-containing domains of ragweed Amb a 1 and mugwort Art v 6 modulate immunologic responses in humans and mice. PLoS One. 2017;12(1):e0169784.
Polukort SH, Rovatti J, Carlson L, et al. IL-10 enhances IgE-mediated mast cell responses and is essential for the development of experimental food allergy in IL-10-deficient mice. J Immunol. 2016;196(12):4865-4876.
Fernandes AMS, da Silva ES, Silveira EF, et al. Recombinant T-cell epitope conjugation: a new approach for Dermatophagoides hypoallergen design. Clin Exp Allergy. 2022. doi:10.1111/cea.14238.
Dougan M, Dranoff G, Dougan SK. GM-CSF, IL-3, and IL-5 family of cytokines: regulators of inflammation. Immunity. 2019;50(4):796-811.
Nagase H, Ueki S, Fujieda S. The roles of IL-5 and anti-IL-5 treatment in eosinophilic diseases: asthma, eosinophilic granulomatosis with polyangiitis, and eosinophilic chronic rhinosinusitis. Allergol Int. 2020;69(2):178-186.
Gour N, Wills-Karp M. IL-4 and IL-13 signaling in allergic airway disease. Cytokine. 2015;75(1):68-78.
Martinez D, Cantillo JF, Herazo H, et al. Characterization of a hybrid protein designed with segments of allergens from Blomia tropicalis and Dermatophagoides pteronyssinus. Immunol Lett. 2018;196:103-112.
Aglas L, Bethanis A, Chrusciel P, et al. In vivo induction of functional inhibitory IgG antibodies by a hypoallergenic Bet v 1 variant. Front Immunol. 2020;11:2118.
Saarne T, Neimert-Andersson T, Gronlund H, Jutel M, Gafvelin G, van Hage M. Treatment with a Fel d 1 hypoallergen reduces allergic responses in a mouse model for cat allergy. Allergy. 2011;66(2):255-263.
Eichhorn S, Horschlager A, Steiner M, et al. Rational design, structure-activity relationship, and immunogenicity of hypoallergenic Pru p 3 variants. Mol Nutr Food Res. 2019;63(18):e1900336.
Alberca Custodio RW, Mirotti L, Gomes E, et al. Dendritic cells expressing MyD88 molecule are necessary and sufficient for CpG-mediated inhibition of IgE production in vivo. Cell. 2019;8(10):1165.
Alberca-Custodio RW, Faustino LD, Gomes E, et al. Allergen-specific immunotherapy with liposome containing CpG-ODN in murine model of asthma relies on MyD88 signaling in dendritic cells. Front Immunol. 2020;11:692.
Abdelaziz MH, Abdelwahab SF, Wan J, et al. Alternatively activated macrophages; a double-edged sword in allergic asthma. J Transl Med. 2020;18(1):58.
Saradna A, Do DC, Kumar S, Fu QL, Gao P. Macrophage polarization and allergic asthma. Transl Res. 2018;191:1-14.
Alves CLS, Santiago LF, Santana MBR, et al. Immunomodulatory properties of Schistosoma mansoni proteins Sm200 and SmKI-1 in vitro and in a murine model of allergy to the mite Blomia tropicalis. Mol Immunol. 2020;124:91-99.
Santos LN, Silva ES, Santos AS, et al. De novo assembly and characterization of the Trichuris trichiura adult worm transcriptome using Ion Torrent sequencing. Acta Trop. 2016;159:132-141.
فهرسة مساهمة: Keywords: Blomia tropicalis; allergen immunotherapy; experimental model; peripheral blood mononuclear cell; vaccine candidate
المشرفين على المادة: 0 (Allergens)
0 (Cytokines)
37341-29-0 (Immunoglobulin E)
تواريخ الأحداث: Date Created: 20230213 Date Completed: 20230811 Latest Revision: 20230824
رمز التحديث: 20231215
DOI: 10.1111/cea.14293
PMID: 36779555
قاعدة البيانات: MEDLINE
الوصف
تدمد:1365-2222
DOI:10.1111/cea.14293