Efficacy, Pharmacokinetics, and Toxicity Profiles of a Broad Anti-SARS-CoV-2 Neutralizing Antibody

• Published in: Viruses Vol. 15; no. 8; p. 1733
• Main Authors: Godínez-Palma, Silvia, González-González, Edith, Ramírez-Villedas, Frida, Garzón-Guzmán, Circe, Vallejo-Castillo, Luis, Carballo-Uicab, Gregorio, Marcelín-Jiménez, Gabriel, Batista, Dany, Pérez-Tapia, Sonia M, Almagro, Juan C
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.08.2023; MDPI
• Subjects: ACE2; Angiotensin; Angiotensin-converting enzyme 2; Animals; Antibodies; Antiviral agents; Chemical properties; COVID-19; Cross-reactivity; Disease; Females; Health aspects; Immunoglobulin G; Infections; Laboratories; Pandemics; Peptidyl-dipeptidase A; Pharmaceutical research; Pharmacokinetics; Physiological aspects; Quarantine; SARS-CoV-2 Delta; SARS-CoV-2 Omicron; Severe acute respiratory syndrome coronavirus 2; therapeutic antibody; Toxicity; toxicology; Transgenic mice; Viral antibodies; Viral diseases; Viruses; Mexico; United States > US
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15081733

We recently reported the isolation and characterization of an anti-SARS-CoV-2 antibody, called IgG-A7, that protects transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from an 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. The PK parameters at these high doses were proportional to the doses, with serum half-life 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 the tissues of these species, supporting the PK/Tox results and suggesting that, while IgG-A7 has a broad efficacy profile, it is not toxic in humans. Thus, the information generated in the CD-1 mice as a PK/Tox model complemented with the mouse and human TCR, could be of relevance as an alternative to Non-Human Primates (NHPs) in rapidly emerging viral diseases and/or quickly evolving viruses such as SARS-CoV-2.