Rapid development of neutralizing and diagnostic SARS-COV-2 mouse monoclonal antibodies
Asheley P. Chapman, Xiaoling Tang, Joo R. Lee, Asiya Seema Chida, Kristina B. Mercer, Rebekah E. Wharton, Markus H. Kainulainen, Jennifer L. Harcourt, Roosecelis B. Martines, Michelle Schroeder, Liangjun Zhao, Anton V. Bryksin, Bin Zhou, Éric Bergeron, Brigid C. Bollweg, Azaibi Tamin, Natalie J. Thornburg, David E. Wentworth, David Petway, Dennis A. Bagarozzi, M. G. Finn, Jason Goldstein
Abstract
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.