Potent SARS-CoV-2 neutralizing antibodies selected from a human antibody library constructed decades ago

Qiang, M.; Ma, P.; Li, Y.; Liu, H.; Harding, A.; Min, C.; Liu, L.; Yuan, M.; Ji, Q.; Tao, P.; Shi, X.; Li, Z.; Wang, F.; Zhang, Y.; Wu, N. C.; Lee, C.-C. D.; Zhu, X.; Gilbert-Jaramillo, J.; Saxena, A.; Huang, X.; Wang, H.; James, W.; Dwek, R. A.; Wilson, I. A.; Yang, G.; Lerner, R. A.

doi:10.1101/2020.11.06.370676

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bioRxiv · 10.1101/2020.11.06.370676

Potent SARS-CoV-2 neutralizing antibodies selected from a human antibody library constructed decades ago

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Abstract

Combinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The SARS-CoV-2 pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, we used a combinatorial human antibody library constructed 20 years before the COVID-19 pandemic to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus. Compared to neutralizing antibodies from COVID-19 patients with generally low somatic hypermutation (SHM), these antibodies contain over 13-22 SHMs, many of which are involved in specific interactions in crystal structures with SARS-CoV-2 spike RBD. The identification of these somatically mutated antibodies in a pre-pandemic library raises intriguing questions about the origin and evolution of human immune responses to SARS-CoV-2.

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Qiang, M., Ma, P., Li, Y., Liu, H., Harding, A., Min, C., Liu, L., Yuan, M., Ji, Q., Tao, P., Shi, X., Li, Z., Wang, F., Zhang, Y., Wu, N. C., Lee, C.-C. D., Zhu, X., Gilbert-Jaramillo, J., Saxena, A., Huang, X., Wang, H., James, W., Dwek, R. A., Wilson, I. A., Yang, G., Lerner, R. A.. 2020-11-06. Potent SARS-CoV-2 neutralizing antibodies selected from a human antibody library constructed decades ago. https://doi.org/10.1101/2020.11.06.370676

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