Academic Journal
Bispecific nanobodies targeting Bet v 1 and ICAM-1 decrease respiratory epithelial penetration of Bet v 1.
| Τίτλος: | Bispecific nanobodies targeting Bet v 1 and ICAM-1 decrease respiratory epithelial penetration of Bet v 1. |
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| Συγγραφείς: | Zettl I; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Ellinger I; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Zghaebi M; Vienna Airway Lab, Department of Otolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria., Jance S; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Izewski V; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Drescher A; Cytiva Europe GmbH, Freiburg, Germany., Breiteneder H; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria., Röck M; Department of Organic Chemistry, University of Innsbruck, Innsbruck, Austria., Tollinger M; Department of Organic Chemistry, University of Innsbruck, Innsbruck, Austria., Eckl-Dorna J; Vienna Airway Lab, Department of Otolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria., Tillib SV; Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia., Flicker S; Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. |
| Πηγή: | Frontiers in immunology [Front Immunol] 2026 Aug 17; Vol. 17, pp. 1864741. Date of Electronic Publication: 2026 Aug 17 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| Ιατρικοί όροι (MeSH): | Intercellular Adhesion Molecule-1*/immunology , Intercellular Adhesion Molecule-1*/metabolism , Antibodies, Bispecific*/immunology , Antibodies, Bispecific*/pharmacology , Antigens, Plant*/immunology , Antigens, Plant*/metabolism , Single-Domain Antibodies*/immunology , Single-Domain Antibodies*/pharmacology , Allergens*/immunology , Respiratory Mucosa*/immunology , Respiratory Mucosa*/metabolism, Epithelial Cells/immunology ; Epithelial Cells/metabolism ; Pollen/immunology ; Humans ; Cell Line |
| Περίληψη: | Background: The major birch pollen allergen Bet v 1 primarily affects the nose and eyes of allergic patients. After crossing the epithelial barrier, it causes IgE-mediated effector cell release, triggering inflammatory responses. We sought to develop bispecific nanobodies that bind Bet v 1 on mucosal surfaces to prevent allergen penetration and subsequent activation of effector cells. Intercellular adhesion molecule 1 (ICAM-1), highly upregulated on epithelial cells of allergic individuals, was chosen as an anchor. Methods: Genetically fused nanobodies targeting Bet v 1 and ICAM-1 were generated and characterized for specificity, affinity, Bet v 1 immobilization on the surface of the human bronchial epithelial cell line, 16HBE14o-, and their potential to inhibit Bet v 1 penetration through a cell monolayer. Results: Bispecific nanobodies recognized ICAM-1, Bet v 1 and related tree pollen allergens (Aln g 1, Cor a 1). While we observed a clear co-localization of nanobodies and Bet v 1 on the 16HBE14o-cell surface after 30 min, Bet v 1 was slightly internalized after 4h at 32 °C. Dissociation rate constants between bispecific nanobodies and antigens were 3-6 times faster at 32 °C compared to 25 °C. Bispecific nanobodies reduced Bet v 1 penetration and hence decreased basophil activation. Conclusion: We generated bivalent nanobodies specific for ICAM-1 and Bet v 1. These nanobodies diminished trans-epithelial transport of Bet v 1 by ICAM-1-mediated immobilization at the cell surface. Reduced Bet v 1 penetration resulted in decreased basophil activation, demonstrating the potential of local administration of nanobodies for the prevention of pollen allergy. (Copyright © 2026 Zettl, Ellinger, Zghaebi, Jance, Izewski, Drescher, Breiteneder, Röck, Tollinger, Eckl-Dorna, Tillib and Flicker.) |
| Competing Interests: | AD was employed by the company Cytiva Europe GmbH. JE-D served as a speaker and/or consultant and/or advisory board member and investigator grants paid to her institution for Sanofi, AstraZeneca and GSK. The remaining authors declare that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors SF and JE-D declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. |
| Σχόλια: | Erratum in: Front Immunol. 2026 Sep 11;17:1974800. doi: 10.3389/fimmu.2026.1974800.. (PMID: 42798949) |
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| Contributed Indexing: | Keywords: ICAM-1; birch pollen allergy; bispecific nanobody; respiratory epithelium; topical treatment |
| Substance Nomenclature: | 126547-89-5 (Intercellular Adhesion Molecule-1) 0 (Antibodies, Bispecific) 0 (Antigens, Plant) 0 (Single-Domain Antibodies) 0 (Allergens) 126161-14-6 (Bet v 1 allergen, Betula) 0 (ICAM1 protein, human) |
| Entry Date(s): | Date Created: 20260901 Date Completed: 20260901 Latest Revision: 20260926 |
| Update Code: | 20260926 |
| PubMed Central ID: | PMC13527034 |
| DOI: | 10.3389/fimmu.2026.1864741 |
| PMID: | 42676692 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1664-3224 |
|---|---|
| DOI: | 10.3389/fimmu.2026.1864741 |