Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Efficacy, Pharmacokinetic and Toxicity Profiles of a Broadly SARS-CoV2 Neutralizing Antibody

Silvia Godínez-Palma
,
Edith González-González
ORCID logo ,
Frida Ramírez-Villedas
,
Circe Garzón-Guzmán
,
Luis Vallejo-Castillo
ORCID logo ,
Gregorio Carballo-Uicab
,
Gabriel Marcelín-Jiménez
,
Dany Batista
,
Sonia M. Pérez-Tapia
* ,
Juan C. Almagro
*
Version 1 : Received: 28 July 2023 / Approved: 31 July 2023 / Online: 1 August 2023 (11:27:40 CEST)

A peer-reviewed article of this Preprint also exists.

Godínez-Palma, S.; González-González, E.; Ramírez-Villedas, F.; Garzón-Guzmán, C.; Vallejo-Castillo, L.; Carballo-Uicab, G.; Marcelín-Jiménez, G.; Batista, D.; Pérez-Tapia, S.M.; Almagro, J.C. Efficacy, Pharmacokinetics, and Toxicity Profiles of a Broad anti-SARS-CoV-2 Neutralizing Antibody. Viruses 2023, 15, 1733. Godínez-Palma, S.; González-González, E.; Ramírez-Villedas, F.; Garzón-Guzmán, C.; Vallejo-Castillo, L.; Carballo-Uicab, G.; Marcelín-Jiménez, G.; Batista, D.; Pérez-Tapia, S.M.; Almagro, J.C. Efficacy, Pharmacokinetics, and Toxicity Profiles of a Broad anti-SARS-CoV-2 Neutralizing Antibody. Viruses 2023, 15, 1733.

Abstract

We recently reported the isolation and characterization of an anti-SARS-CoV-2 antibody, called IgG-A7, that protected transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from the infection with SARS-CoV-2 Wuhan. We show here that IgG-A7 protected 100% of the transgenic mice infected with Delta (B.1.617.2) and Omicron (B.1.1.529) at doses of 0.5 and 5 mg/kg, respectively. In addition, we studied the pharmacokinetic (PK) profile and Toxicology (Tox) of IgG-A7 in CD-1 mice at single doses of 100 and 200 mg/kg. PK parameters at those high doses were proportional to the dose, with the half-life in serum of ~10.5 days. IgG-A7 was well tolerated with no signs of toxicity in urine and blood samples, nor in histopathology analyses. Tissue Cross-reactivity (TCR) with a panel of mouse and human tissues showed no evidence of IgG-A7 interaction with tissues of these species, supporting the PK/Tox results in vivo and suggesting that while IgG-A7 has a broad efficacy profile it is not toxic in humans. The information generated in CD-1 mouse as PK/Tox model, complemented with the mouse and human TCR, could be of relevance as alternatives to NHPs in rapidly emerging viral diseases and/or quickly evolving viruses such as SARS-CoV-2.

Keywords

COVID-19; therapeutic antibody; SARS-CoV-2 Delta; SARS-CoV-2 Omicron; toxicology

Subject

Biology and Life Sciences, Biology and Biotechnology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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