Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding

Clarissa Bauernfeind, Ines Zettl, Tatiana Ivanova, Oksana Goryainova, Anna Marianne Weijler, Barbara Pranz, Anja Drescher, Margarete Focke-Tejkl, Tea Pavkov-Keller, Julia Eckl-Dorna, Sergei V Tillib, Sabine Flicker

Research output: Journal article (peer-reviewed)Journal article

Abstract

BACKGROUND: Around 20% of the population in Northern and Central Europe is affected by birch pollen allergy, with the major birch pollen allergen Bet v 1 as the main elicitor of allergic reactions. Together with its cross-reactive allergens from related trees and foods, Bet v 1 causes an impaired quality of life. Hence, new treatment strategies were elaborated, demonstrating the effectiveness of blocking IgG antibodies on Bet v 1-induced IgE-mediated reactions. A recent study provided evidence for the first time that Bet v 1-specific nanobodies reduce patients´ IgE binding to Bet v 1. In order to increase the potential to outcompete IgE recognition of Bet v 1 and to foster cross-reactivity and cross-protection, we developed Bet v 1-specific nanobody trimers and evaluated their capacity to suppress polyclonal IgE binding to corresponding allergens and allergen-induced basophil degranulation.

METHODS: Nanobody trimers were engineered by adding isoleucine zippers, thus enabling trimeric formation. Trimers were analyzed for their cross-reactivity, binding kinetics to Bet v 1, and related allergens, and patients' IgE inhibition potential. Finally, their efficacy to prevent basophil degranulation was investigated.

RESULTS: Trimers showed enhanced recognition of cross-reactive allergens and increased efficiency to reduce IgE-allergen binding compared to nanobody monomers. Furthermore, trimers displayed slow dissociation rates from allergens and suppressed allergen-induced mediator release.

CONCLUSION: We generated high-affine nanobody trimers that target Bet v 1 and related allergens. Trimers blocked IgE-allergen interaction by competing with IgE for allergen binding. They inhibited IgE-mediated release of biological mediators, demonstrating a promising potential to prevent allergic reactions caused by Bet v 1 and relatives.

Original languageEnglish
Article number1343024
Pages (from-to)1343024
JournalFrontiers in Immunology
Volume15
DOIs
Publication statusPublished - May 2024

Keywords

  • Immunoglobulin E/immunology
  • Humans
  • Antigens, Plant/immunology
  • Single-Domain Antibodies/immunology
  • Cross Reactions/immunology
  • Allergens/immunology
  • Basophils/immunology
  • Protein Binding
  • Rhinitis, Allergic, Seasonal/immunology
  • Protein Multimerization

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