Potent mouse monoclonal antibodies that block SARS-CoV-2 infection

Youjia Guo,Atsushi Kawaguchi,Masaru Takeshita,Takeshi Sekiya,Mikako Hirohama,Akio Yamashita,Haruhiko Siomi,Kensaku Murano

doi:10.1016/j.jbc.2021.100346

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has developed into a global pandemic since its first outbreak in the winter of 2019. An extensive investigation of SARS-CoV-2 is critical for disease control. Various recombinant monoclonal antibodies of human origin that neutralize SARS-CoV-2 infection have been isolated from convalescent patients and will be applied as therapies and prophylaxis. However, the need for dedicated monoclonal antibodies suitable for molecular pathology research is not fully addressed. Here, we produced six mouse anti-SARS-CoV-2 spike monoclonal antibodies that not only exhibit robust performance in immunoassays including western blotting, ELISA, immunofluorescence, and immunoprecipitation, but also demonstrate neutralizing activity against SARS-CoV-2 infection to VeroE6/TMPRSS2 cells. Due to their mouse origin, our monoclonal antibodies are compatible with the experimental immunoassay setups commonly used in basic molecular biology research laboratories, providing a useful tool for future research. Furthermore, in the hope of applying the antibodies of clinical setting, we determined the variable regions of the antibodies and used them to produce recombinant human/mouse chimeric antibodies.

Highlights

With the development of humanized mouse antibodies and subsequent generation of fully human antibodies by various techniques, monoclonal antibodies have become widely used in therapy and prophylaxis for cancer, autoimmune diseases, and viral pathogens [3]
The SARS-CoV-2 spike glycoprotein is a homotrimeric fusion protein composed of two subunits: S1 and S2
The receptor-binding domain (RBD) on S1 subunit binds to angiotensinconverting enzyme 2 (ACE2), resulting in destabilization of the spike protein’s metastable conformation

Summary

Introduction

With the development of humanized mouse antibodies and subsequent generation of fully human antibodies by various techniques, monoclonal antibodies have become widely used in therapy and prophylaxis for cancer, autoimmune diseases, and viral pathogens [3]. We established six monoclonal antibodies against the spike glycoprotein of SARS-CoV-2. ACCELERATED COMMUNICATION: Mouse anti-SARS-CoV-2 spike monoclonal antibody

Results

Conclusion