Non-clinical safety assessment and in vivo biodistribution of CoviFab, an RBD-specific F(ab')2 fragment derived from equine polyclonal antibodies
| Autor: | Fernando Alberto Goldbaum, Belkis Ester Marelli, Luciana Muñoz, Ulises Sebastián Notaro, Santiago Sanguineti, Paula Silvestrini, Hugo Hector Ortega, Facundo José Salinas, Lucas Etchevers, Vanesa Zylberman, Natalia Raquel Salvetti |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Biodistribution Preclinical studies Mice Transgenic Pharmacology Toxicology Antibodies Viral Article Mice In vivo Internal medicine medicine Animals Humans Tissue Distribution Horses Receptors Immunologic Adverse effect Mice Inbred BALB C Hematology Spectroscopy Near-Infrared Good laboratory practices biology Clinical pathology business.industry SARS-CoV-2 COVID-19 Recombinant Proteins COVID-19 Drug Treatment CoviFab HEK293 Cells Polyclonal antibodies biology.protein Histopathology Administration Intravenous business Ex vivo |
| Zdroj: | Toxicology and Applied Pharmacology |
| ISSN: | 1096-0333 |
| Popis: | The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has required the urgent development of new therapies, among which passive immunotherapy is contemplated. CoviFab (INM005) is a RBD-specific F(ab′)2 fragment derived from equine polyclonal antibodies. We investigate their preclinical security and biodistribution by in vivo and ex vivo NIR imaging after intravenous administration of a dose of 4 mg/kg at time 0 and 48 h. Images were taken at 1, 12, 24, 36, 48, 49, 60, 72, 84, 96, 108, 120, 132 and 144 h after the first intravenous injection. At 96 and 144 h, mice were sacrificed for haematology, serum chemistry, clinical pathology, histopathology and ex vivo imaging. The biodistribution profile was similar in all organs studied, with the highest fluorescence at 1 h after each injection, gradually decreasing after that each one and until the end of the study (144 h). The toxicology study revealed no significant changes in the haematology and serum chemistry parameters. Further, there were no changes in the gross and histological examination of organs. Nonclinical data of the current study confirm that CoviFab is safe, without observable adverse effects in mice. Furthermore, we confirm that bioimaging studies are a useful approach in preclinical trials to determine biodistribution. Graphical abstract Unlabelled Image |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect