A hybrid of two major Blomia tropicalis allergens as an allergy vaccine candidate

Eduardo Santos da Silva, Lorenz Aglas, Carina Silva Pinheiro, Emília M M de Andrade Belitardo, Elisânia Fontes Silveira, Sara Huber, Rogério Tanan Torres, Michael Wallner, Peter Briza, Peter Lackner, Josef Laimer, Luis Gustavo C Pacheco, Álvaro A Cruz, Neuza Maria Alcântara-Neves, Fatima Ferreira

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalClinical and Experimental Allergy
DOIs
Publication statusE-pub ahead of print - 20 Apr 2020

Bibliographical note

© 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Fields of Science and Technology Classification 2012

  • 303 Health Sciences

Cite this

da Silva, E. S., Aglas, L., Pinheiro, C. S., de Andrade Belitardo, E. M. M., Silveira, E. F., Huber, S., Torres, R. T., Wallner, M., Briza, P., Lackner, P., Laimer, J., Pacheco, L. G. C., Cruz, Á. A., Alcântara-Neves, N. M., & Ferreira, F. (2020). A hybrid of two major Blomia tropicalis allergens as an allergy vaccine candidate. Clinical and Experimental Allergy. https://doi.org/10.1111/cea.13611