Development of an inhibiting antibody against equine interleukin 5 to treat insect bite hypersensitivity of horses

authored by
Nora Langreder, Dorina Schäckermann, Doris Meier, Marlies Becker, Maren Schubert, Stefan Dübel, Thomas Reinard, Stefanie Figge‑Wegener, Kristine Roßbach, Wolfgang Bäumler, Simone Ladel, Michael Hust
Abstract

Insect bite hypersensitivity (IBH) is the most common allergic skin disease of horses. It is caused by insect bites of the Culicoides spp. which mediate a type I/IVb allergy with strong involvement of eosinophil cells. No specific treatment option is available so far. One concept could be the use of a therapeutic antibody targeting equine interleukin 5, the main activator and regulator of eosinophils. Therefore, antibodies were selected by phage display using the naïve human antibody gene libraries HAL9/10, tested in a cellular in vitro inhibition assay and subjected to an in vitro affinity maturation. In total, 28 antibodies were selected by phage display out of which eleven have been found to be inhibiting in the final format as chimeric immunoglobulin G with equine constant domains. The two most promising candidates were further improved by in vitro affinity maturation up to factor 2.5 regarding their binding activity and up to factor 2.0 regarding their inhibition effect. The final antibody named NOL226-2-D10 showed a strong inhibition of the interleukin 5 binding to its receptor (IC

50 = 4 nM). Furthermore, a nanomolar binding activity (EC

50 = 8.8 nM), stable behavior and satisfactory producibility were demonstrated. This antibody is an excellent candidate for in vivo studies for the treatment of equine IBH.

Organisation(s)
Section Plant Biotechnology
External Organisation(s)
Freie Universität Berlin
Technische Universität Braunschweig
Novihum Technologies GmbH
Wirtschaftsgenossenschaft deutscher Tierärzte eG (WDT)
Type
Article
Journal
Scientific Reports
Volume
13
ISSN
2045-2322
Publication date
10.03.2023
Publication status
Published
Peer reviewed
Yes
ASJC Scopus subject areas
General
Sustainable Development Goals
SDG 3 - Good Health and Well-being
Electronic version(s)
https://doi.org/10.1038/s41598-023-31173-y (Access: Open)