In Vitro and In Vivo Characterization of a Broadly Neutralizing Anti-SARS-CoV-2 Antibody Isolated from a Semi-Immune Phage Display Library

Abstract

Neutralizing antibodies targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and/or treat COVID-19. However, as SARS-CoV-2 has evolved into new variants, most of the neutralizing antibodies authorized by the US FDA and/or EMA to treat COVID-19 have shown reduced efficacy or have failed to neutralize the variants of concern (VOCs), particularly B.1.1.529 (Omicron). Previously, we reported the discovery and characterization of antibodies with high affinity for SARS-CoV-2 RBD Wuhan (WT), B.1.617.2 (Delta), and B.1.1.529 (Omicron) strains. One of the antibodies, called IgG-A7, also blocked the interaction of human angiotensin-converting enzyme 2 (hACE2) with the RBDs of the three strains, suggesting it may be a broadly SARS-CoV-2 neutralizing antibody. Herein, we show that IgG-A7 efficiently neutralizes all the three SARS-CoV-2 strains in plaque reduction neutralization tests (PRNTs). In addition, we demonstrate that IgG-A7 fully protects K18-hACE2 transgenic mice infected with SARS-CoV-2 WT. Taken together, our findings indicate that IgG-A7 could be a suitable candidate for development of antibody-based drugs to treat and/or prevent SARS-CoV-2 VOCs infection.

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

“…However, it decreased significantly in the group treated with 5 mg/kg ( p = 0.001), indicating a protective effect at that higher dose. The efficacy of IgG-A7 at 0.5 mg/kg against Delta infection and a ten-fold higher dose (5 mg/kg) against Omicron correlated with the neutralization potency of IgG-A7 in PRNT [ 6 ], showing that IgG-A7 had a lower NC 50 for Omicron (2.93 nM) than for Delta (0.06 nM).…”

“…The SARS-CoV-2 Delta and Omicron viruses were isolated and characterized as described in González-González [ 6 ]. The whole genome sequences of these SARS-CoV-2 strains are deposited in GenBank with the following accession numbers: OM060237 (Delta) and ON651664 (Omicron).…”

“…In a previous work [ 5 , 6 ], we reported the isolation of an antibody called IgG-A7 that neutralized the WT, Delta (B.1.617.2), and Omicron strains in plaque reduction neutralization tests (PRNTs) with authentic viruses. IgG-A7 also protected transgenic K18-hACE2 mice for the hACE-2 from a SARS-CoV-2 WT infection at a dose of 5 mg/kg [ 6 ]. In this work, we expanded the efficacy studies of IgG-A7 in K18-hACE2 mice infected with Delta and Omicron at doses of 0.5 and 5 mg/kg.…”

Identification of SARS-CoV-2 Main Protease Inhibitors Using Chemical Similarity Analysis Combined with Machine Learning

“…In vitro viral neutralization assays were performed as previously described [ 92 ] using a clinical isolate of SARS-CoV-2 (GenBank: OL790194). Briefly, cultures of Vero CCL81 cells (50,000 cells/cm 2 ) were seeded into 24-well plates, and the next day, the cells were exposed for 1 h to subtoxic concentrations of the Mpro inhibitors prepared in serum-free EMEM.…”

Development of a Single-Chain Fragment Variable that Binds to the SARS-CoV-2 Spike Protein Produced by Genetically Modified Lactic Acid Bacteria

“…An antibody cocktail therapy targeting the RBD has achieved specific results [ 7 ]. Indeed, Mendoza-Salazar and González-González et al reported that a phage display single-chain fragment variable (scFv) blocks binding of the RBD to human ACE2, suggesting these antibodies may neutralize SARS-CoV-2 infection [ 8 , 9 ].…”