Murine Monoclonal Antibodies against the Receptor Binding Domain of SARS-CoV-2 Neutralize Authentic Wild-Type SARS-CoV-2 as Well as B.1.1.7 and B.1.351 Viruses and Protect In Vivo in a Mouse Model in a Neutralization-Dependent Manner.

After first emerging in late 2019 in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has since caused a pandemic leading to millions of infections and deaths worldwide. Vaccines have been developed and authorized, but the supply of these vaccines is currently limited. With new variants of the virus now emerging and spreading globally, it is essential to develop therapeutics that are broadly protective and bind conserved epitopes in the receptor binding domain (RBD) or the full-length spike protein of SARS-CoV-2. In this study, we generated mouse monoclonal antibodies (MAbs) against different epitopes on the RBD and assessed binding and neutralization of authentic SARS-CoV-2. We demonstrate that antibodies with neutralizing activity, but not nonneutralizing antibodies, lower viral titers in the lungs when administered in a prophylactic setting in vivo in a mouse challenge model. In addition, most of the MAbs cross-neutralize the B.1.351 as well as the B.1.1.7 variant in vitro. IMPORTANCE Cross-neutralization of SARS-CoV-2 variants by RBD-targeting antibodies is still not well understood, and very little is known about the potential protective effect of nonneutralizing antibodies in vivo. Using a panel of mouse monoclonal antibodies, we investigate both of these points.