Rapid Development of Neutralizing and Diagnostic SARS-COV-2 Mouse Monoclonal Antibodies

Chapman, A. P.; Tang, X.; Lee, J. R.; Chida, A.; Mercer, K.; Wharton, R. E.; Kainulainen, M. H.; Harcourt, J. L.; Martines, R. B.; Schroeder, M.; Zhao, L.; Bryksin, A.; Zhou, B.; Bergeron, E.; Bollweg, B. C.; Tamin, A.; Thornburg, N.; Wentworth, D. E.; Petway, D.; Bagarozzi, D.; Finn, M. G.; Goldstein, J. M.

doi:10.1101/2020.10.13.338095

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bioRxiv · 10.1101/2020.10.13.338095

Rapid Development of Neutralizing and Diagnostic SARS-COV-2 Mouse Monoclonal Antibodies

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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 nanomolar-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.

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Chapman, A. P., Tang, X., Lee, J. R., Chida, A., Mercer, K., Wharton, R. E., Kainulainen, M. H., Harcourt, J. L., Martines, R. B., Schroeder, M., Zhao, L., Bryksin, A., Zhou, B., Bergeron, E., Bollweg, B. C., Tamin, A., Thornburg, N., Wentworth, D. E., Petway, D., Bagarozzi, D., Finn, M. G., Goldstein, J. M.. 2020-10-14. Rapid Development of Neutralizing and Diagnostic SARS-COV-2 Mouse Monoclonal Antibodies. https://doi.org/10.1101/2020.10.13.338095

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