Post-exposure protection of SARS-CoV-2 lethal infected K18-hACE2 transgenic mice by neutralizing human monoclonal antibody

Abstract

Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits high levels of mortality and morbidity and has dramatic consequences on human live, sociality and global economy. Neutralizing antibodies constitute a highly promising approach for treating and preventing infection by this novel pathogen. In the present study, we characterized and further evaluated the recently identified human monoclonal MD65 antibody for its ability to provide protection against a lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice. 75% of the untreated mice succumbed 6-9 days post-infection while administration of the MD65 antibody as late as 3 days after exposure, rescued all infected animals. The data unprecedentedly demonstrate, the therapeutic value of human monoclonal antibodies as a life-saving treatment of severe COVID-19 infection.

Therapeutic antibodies, targeting the SARS-CoV-2 spike N-terminal domain, protect lethally infected K18-hACE2 mice

“…All treated mice revealed elicitation of immune responses against the three tested antigens. This result is in a good agreement with our previous observation, using anti-RBD mAb 14 . In this previous report, endogenous response, following treatment with high mAb dose, was shown to correlate with time of treatment, demonstrating a marked response in post-exposure treatment, rather than in prophylactic one.…”

“…This model was recently shown to fatefully recapitulate the SARS-CoV-2 infection and consequently to serve as a reliable model to predict the efficacy of therapeutic strategies 35,38 36,38,39 . In a recent study, we applied this model for demonstration of the protection efficacy of therapeutic mAb directed to the S1-RBD, when administered 2 days post-infection (dpi) 14 .…”

The neutralization potency of anti-SARS-CoV-2 therapeutic human monoclonal antibodies is retained against novel viral variants

“…The copyright holder for this preprint (which this version posted April 5, 2021. ; https://doi.org/10.1101/2021.04.01.438035 doi: bioRxiv preprint Of note, the anti-RBD antibody MD65, shown here to retain its neutralizing potential against emerging variants, was recently suggested by extensive pre-clinical studies to be an important therapeutic product for efficient clinical intervention in COVID-19 cases (Rosenfeld et al, 2021).…”

“…The SARS-CoV-2 spike (S) stabilized soluble ectodomain, S1 subunit (WT rS1) and receptor binding domain (WT rRBD) were produced as previously described (Noy-Porat et al, 2020 All antibodies (except LY-CoV555) were produced as full IgG1 antibodies as described (Barlev-Gross et al, 2021;Rosenfeld et al, 2021), expressed using ExpiCHO TM Expression system (Thermoscientific, USA) and purified on HiTrap Protein-A column (GE . CC-BY-NC-ND 4.0 International license available under a was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

“…We previously reported the isolation of RBD-and NTD-specific mAbs (Barlev-Gross et al, 2021;Noy-Porat et al, 2020;Noy-Porat et al, 2021;Rosenfeld et al, 2021), among which the MD65 mAb showing exceptional neutralization potency, as demonstrated by in vitro and in vivo experiments. In the current study, we present the re-evaluation of four SARS-CoV-2 neutralizing mAbs (MD65, MD62, MD29 and BL6), directed against 4 distinct epitopes in the spike RBD, for their ability to bind recombinant RBD proteins, individually representing substitutions encountered in the VOCs.…”