Rapid development of neutralizing and diagnostic SARS-COV-2 mouse monoclonal antibodies

Chapman, Asheley P.; Tang, Xiaoling; Lee, Joo R.; Chida, Asiya; Mercer, Kristina; Wharton, Rebekah E.; Kainulainen, Markus; Harcourt, Jennifer L.; Martines, Roosecelis B.; Schroeder, Michelle; Zhao, Liangjun; Bryksin, Anton; Zhou, Bin; Bergeron, Eric; Bollweg, Brigid C.; Tamin, Azaibi; Thornburg, Natalie; Wentworth, David E.; Petway, David; Bagarozzi, Dennis A.; Finn, M. G.; Goldstein, Jason M.

The need for high-affinity, SARS-CoV-2-specific monoclonal antibodies (mAbs) is critical in the face of the global COVID-19 pandemic, as such reagents can have important diagnostic, research, and therapeutic applications. Of greatest interest is the ~ 300 amino acid receptor binding domain (RBD) within the S1 subunit of the spike protein because of its key interaction with the human angiotensin converting enzyme 2 (hACE2) receptor present on many cell types, especially lung epithelial cells. We report here the development and functional characterization of 29 nM-affinity mouse SARS-CoV-2 mAbs created by an accelerated immunization and hybridoma screening process. Differing functions, including binding of diverse protein epitopes, viral neutralization, impact on RBD-hACE2 binding, and immunohistochemical staining of infected lung tissue, were correlated with variable gene usage and sequence.