Details
| Originalsprache | Englisch |
|---|---|
| Aufsatznummer | 4029 |
| Fachzeitschrift | Scientific Reports |
| Jahrgang | 13 |
| Ausgabenummer | 1 |
| Publikationsstatus | Veröffentlicht - 10 März 2023 |
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.
ASJC Scopus Sachgebiete
Ziele für nachhaltige Entwicklung
Zitieren
- Standard
- Harvard
- Apa
- Vancouver
- BibTex
- RIS
in: Scientific Reports, Jahrgang 13, Nr. 1, 4029, 10.03.2023.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Development of an inhibiting antibody against equine interleukin 5 to treat insect bite hypersensitivity of horses
AU - Langreder, Nora
AU - Schäckermann, Dorina
AU - Meier, Doris
AU - Becker, Marlies
AU - Schubert, Maren
AU - Dübel, Stefan
AU - Reinard, Thomas
AU - Figge‑Wegener, Stefanie
AU - Roßbach, Kristine
AU - Bäumler, Wolfgang
AU - Ladel, Simone
AU - Hust, Michael
PY - 2023/3/10
Y1 - 2023/3/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85150006817&partnerID=8YFLogxK
U2 - 10.1038/s41598-023-31173-y
DO - 10.1038/s41598-023-31173-y
M3 - Article
VL - 13
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 4029
ER -