Discovery and Development of Human SARS-CoV-2 Neutralizing Antibodies using an Unbiased Phage Display Library Approach

Cao, X.; Maruyama, J.; Zhou, H.; Kerwin, L.; Sattler, R.; Manning, J. T.; Johnson, S.; Richards, S.; Blair, B.; Du, N.; Morais, K.; Lawrence, K.; Lu, L.; Pai, C.-I.; Li, D.; Brunswick, M.; Zhang, Y.; Ji, H.; Paessler, S.; Allen, R. D.

doi:10.1101/2020.09.27.316174

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bioRxiv · 10.1101/2020.09.27.316174

Discovery and Development of Human SARS-CoV-2 Neutralizing Antibodies using an Unbiased Phage Display Library Approach

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Abstract

SARS-CoV-2 neutralizing antibodies represent an important component of the ongoing search for effective treatment of and protection against COVID-19. We report here on the use of a naive phage display antibody library to identify a panel of fully human SARS-CoV-2 neutralizing antibodies. Following functional profiling in vitro against an early pandemic isolate as well as a recently emerged isolate bearing the D614G Spike mutation, the clinical candidate antibody, STI-1499, and the affinity-engineered variant, STI-2020, were evaluated for in vivo efficacy in the Syrian golden hamster model of COVID-19. Both antibodies demonstrated potent protection against the pathogenic effects of the disease and a dose-dependent reduction of virus load in the lungs, reaching undetectable levels following a single dose of 500 micrograms of STI-2020. These data support continued development of these antibodies as therapeutics against COVID-19 and future use of this approach to address novel emerging pandemic disease threats.

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Cao, X., Maruyama, J., Zhou, H., Kerwin, L., Sattler, R., Manning, J. T., Johnson, S., Richards, S., Blair, B., Du, N., Morais, K., Lawrence, K., Lu, L., Pai, C.-I., Li, D., Brunswick, M., Zhang, Y., Ji, H., Paessler, S., Allen, R. D.. 2020-09-28. Discovery and Development of Human SARS-CoV-2 Neutralizing Antibodies using an Unbiased Phage Display Library Approach. https://doi.org/10.1101/2020.09.27.316174

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