4.6 Article

Isolation of nanobodies with potential to reduce patients' IgE binding to Bet v 1

Journal

ALLERGY
Volume 77, Issue 6, Pages 1751-1760

Publisher

WILEY
DOI: 10.1111/all.15191

Keywords

allergy; Bet v 1; IgE; nanobody; VHH

Funding

  1. Austrian Science Fund (FWF) [I3946-B33, F4607, P32953]
  2. Russian Foundation for Basic Research (RFBR) [18-515-14003]
  3. Austrian Science Fund (FWF) [P32953] Funding Source: Austrian Science Fund (FWF)

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The study identified high-affinity Bet v 1-specific nanobodies that can recognize an important IgE epitope and reduce allergen-induced basophil activation, indicating that allergen-specific nanobodies are useful tools for future treatment of pollen allergy.
Background Recent studies showed that a single injection of human monoclonal allergen-specific IgG antibodies significantly reduced allergic symptoms in birch pollen-allergic patients. Since the production of full monoclonal antibodies in sufficient amounts is laborious and expensive, we sought to investigate if smaller recombinant allergen-specific antibody fragments, that is, nanobodies, have similar protective potential. For this purpose, nanobodies specific for Bet v 1, the major birch pollen allergen, were generated to evaluate their efficacy to inhibit IgE-mediated responses. Methods A cDNA-VHH library was constructed from a camel immunized with Bet v 1 and screened for Bet v 1 binders encoding sequences by phage display. Selected nanobodies were expressed, purified, and analyzed in regards of epitope-specificity and affinity to Bet v 1. Furthermore, cross-reactivity to Bet v 1-homologues from alder, hazel and apple, and their usefulness to inhibit IgE binding and allergen-induced basophil activation were investigated. Results We isolated three nanobodies that recognize Bet v 1 with high affinity and cross-react with Aln g 1 (alder) and Cor a 1 (hazel). Their epitopes were mapped to the alpha-helix at the C-terminus of Bet v 1. All nanobodies inhibited allergic patients' polyclonal IgE binding to Bet v 1, Aln g 1, and Cor a 1 and partially suppressed Bet v 1-induced basophil activation. Conclusion We identified high-affinity Bet v 1-specific nanobodies that recognize an important IgE epitope and reduce allergen-induced basophil activation revealing the first proof that allergen-specific nanobodies are useful tools for future treatment of pollen allergy.

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