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Generation of high affinity ICAM-1-specific nanobodies and evaluation of their suitability for allergy treatment

Ines Zettl, Tatiana Ivanova, Mohammed Zghaebi, Marina V. Rutovskaya, Isabella Ellinger, Oksana Goryainova, Jessica Kollárová, Sergio Villazala-Merino, Christian Lupinek, Christina Weichwald, Anja Drescher, Julia Eckl-Dorna,...[more]

 

Nothobranchius furzeri, the Turquoise Killifish: A Model of Age-Related Osteoporosis?

Maria Butylina, PhD-student in the group of Prof. Dr. Peter Pietschmann, published recently her research on Nothobranchius furzeri, the turquoise killifish, in Gerontology. [more]

 

Isolation of nanobodies with potential to reduce patients' IgE binding to the major birch pollen allergen, Bet v 1

Ines Zettl, Tatiana Ivanova, Maria R. Strobl, Christina Weichwald, Oksana Goryainova, Evgenia Khan, Marina V. Rutovskaya, Margarete Focke- Tejkl, Anja Drescher, Barbara Bohle, Sabine Flicker, Sergei V. Tillib Allergy 2022...[more]

 

Impaired Mineral Ion Metabolism in a Mouse Model of Targeted Calcium-Sensing Receptor (CaSR) Deletion from Vascular Smooth Muscle Cells

Martin Schepelmann (group Enikö Kallay) and national and international colleagues and collaborators have just published a study in the Journal of the American Society of Nephrology (JASN), one of the highest ranked and most...[more]

 

Vaccine based on folded RBD-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants

The preclinical data for a vaccine developed at MedUni Vienna to protect against SARS-CoV-2 indicates that it is effective against all SARS-CoV-2 variants known to date, including omicron - even in those who have not yet built up...[more]

 

Birch pollen allergic patients have IgE and IgG antibodies binding to diverse patterns of conformational epitopes on the major allergen, Bet v 1

Schmalz S, Mayr V, Shosherova A, Gepp B, Ackerbauer D, Sturm G, Bohle B, Breiteneder H, Radauer C. Isotype-specific binding patterns of serum antibodies to multiple conformational epitopes of Bet v 1.[more]

 

Neutralization of SARS-CoV-2 requires antibodies against conformational receptor-binding domain epitopes.

Gattinger P, Niespodziana K, Stiasny K, Sahanic S, Tulaeva I, Borochova K, Dorofeeva Y, Schlederer T, Sonnweber T, Hofer G, Kiss R, Kratzer B, Trapin D, Tauber PA, Rottal A, Körmöczi U, Feichter M, Weber M, Focke-Tejkl M,...[more]

 
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Inhaltsbereich

Generation of high affinity ICAM-1-specific nanobodies and evaluation of their suitability for allergy treatment

Ines Zettl, Tatiana Ivanova, Mohammed Zghaebi, Marina V. Rutovskaya, Isabella Ellinger, Oksana Goryainova, Jessica Kollárová, Sergio Villazala-Merino, Christian Lupinek, Christina Weichwald, Anja Drescher, Julia Eckl-Dorna, Sergei V. Tillib, Sabine Flicker.


Front Immunol. 2022 Nov 9;13:1022418.
doi: 10.3389/fimmu.2022.1022418

 

Pollen allergy is considered one of the most common IgE-mediated hypersensitivity disorders and represents a global health and economic burden. The nose is an important site of allergen entry, where trans-epithelial allergen penetration and subsequent IgE-mediated allergic inflammation can potentially be inhibited. Topically applied allergen-specific IgG antibodies that are able to catch allergens on the apical side and efficiently block allergen penetration of the epithelial barrier have been reported. These antibodies were chemically conjugated to IgG antibodies specific for Intercellular Adhesion Molecule 1 (ICAM-1), a molecule highly expressed during allergic inflammation, to anchor them to the apical side of epithelial cells. To produce well defined antibody constructs at reasonable expenses, we were interested to generate nanobody-based constructs specific for ICAM-1 and allergens. We have previously characterized nanobodies specific for the major birch pollen allergen Bet v 1 and here we report the generation and characterization of ICAM-1-specific nanobodies.

Nanobodies were obtained from a camel immunized with ICAM-1 and a strong binder was selected after phage display. The isolated nanobody (Nb44) specifically recognized ICAM-1 expressed on the human bronchial epithelial cell line 16HBE14o-, our surrogate for the nasal cavity. More importantly, Nb44 was not internalized upon ICAM-1 binding (up to 24 hours). Additionally, it displayed high affinity to ICAM-1 and slow off-rates comparable to monoclonal IgG antibodies.

These characteristics (high affinity to ICAM-1 and lack of internalization) render our isolated nanobody a suitable candidate to engineer heterodimers with allergen-specific nanobodies in order to develop topical treatments of pollen allergy.

This study was supported by the Austrian Science Fund (FWF) grants I3946-B33 and F4607, by the Russian Foundation for Basic Research (RFBR) grant 18-515-14003 and by the Country of Lower Austria’s funded Danube Allergy Research Cluster.

 
 
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