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Non-clinical safety assessment and in vivo biodistribution of CoviFab, an RBD-specific F(ab′)2 fragment derived from equine polyclonal antibodies
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 se...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590615/ https://www.ncbi.nlm.nih.gov/pubmed/34785274 http://dx.doi.org/10.1016/j.taap.2021.115796 |
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author | Salinas, Facundo Marelli, Belkis E. Sanguineti, Santiago Goldbaum, Fernando Muñoz, Luciana Etchevers, Lucas Silvestrini, Paula Notaro, Ulises S. Salvetti, Natalia R. Zylberman, Vanesa Ortega, Hugo H. |
author_facet | Salinas, Facundo Marelli, Belkis E. Sanguineti, Santiago Goldbaum, Fernando Muñoz, Luciana Etchevers, Lucas Silvestrini, Paula Notaro, Ulises S. Salvetti, Natalia R. Zylberman, Vanesa Ortega, Hugo H. |
author_sort | Salinas, Facundo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8590615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85906152021-11-15 Non-clinical safety assessment and in vivo biodistribution of CoviFab, an RBD-specific F(ab′)2 fragment derived from equine polyclonal antibodies Salinas, Facundo Marelli, Belkis E. Sanguineti, Santiago Goldbaum, Fernando Muñoz, Luciana Etchevers, Lucas Silvestrini, Paula Notaro, Ulises S. Salvetti, Natalia R. Zylberman, Vanesa Ortega, Hugo H. Toxicol Appl Pharmacol Article 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. Elsevier Inc. 2022-01-01 2021-11-14 /pmc/articles/PMC8590615/ /pubmed/34785274 http://dx.doi.org/10.1016/j.taap.2021.115796 Text en © 2021 Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Salinas, Facundo Marelli, Belkis E. Sanguineti, Santiago Goldbaum, Fernando Muñoz, Luciana Etchevers, Lucas Silvestrini, Paula Notaro, Ulises S. Salvetti, Natalia R. Zylberman, Vanesa Ortega, Hugo H. Non-clinical safety assessment and in vivo biodistribution of CoviFab, an RBD-specific F(ab′)2 fragment derived from equine polyclonal antibodies |
title | Non-clinical safety assessment and in vivo biodistribution of CoviFab, an RBD-specific F(ab′)2 fragment derived from equine polyclonal antibodies |
title_full | Non-clinical safety assessment and in vivo biodistribution of CoviFab, an RBD-specific F(ab′)2 fragment derived from equine polyclonal antibodies |
title_fullStr | Non-clinical safety assessment and in vivo biodistribution of CoviFab, an RBD-specific F(ab′)2 fragment derived from equine polyclonal antibodies |
title_full_unstemmed | Non-clinical safety assessment and in vivo biodistribution of CoviFab, an RBD-specific F(ab′)2 fragment derived from equine polyclonal antibodies |
title_short | Non-clinical safety assessment and in vivo biodistribution of CoviFab, an RBD-specific F(ab′)2 fragment derived from equine polyclonal antibodies |
title_sort | non-clinical safety assessment and in vivo biodistribution of covifab, an rbd-specific f(ab′)2 fragment derived from equine polyclonal antibodies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590615/ https://www.ncbi.nlm.nih.gov/pubmed/34785274 http://dx.doi.org/10.1016/j.taap.2021.115796 |
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