Discovery and development of human SARS-CoV-2 neutralizing antibodies using an unbiased phage display library approach

Xia Cao; Junki Maruyama; Heyue Zhou; Lisa Kerwin; Rachel Sattler; John T. Manning; Sachi Johnson; Susan Richards; Yan Li; Weiqun Shen; Benjamin Blair; Na Du; Kyndal Morais; Kate Lawrence; Lucy Lu; Chin I. Pai; Donghui Li; Mark Brunswick; Yanliang Zhang; Henry Ji; Slobodan Paessler; Robert D. Allen

doi:10.1101/2020.09.27.316174

Discovery and development of human SARS-CoV-2 neutralizing antibodies using an unbiased phage display library approach

Xia Cao, Junki Maruyama, Heyue Zhou, Lisa Kerwin, Rachel Sattler, John T. Manning, Sachi Johnson, Susan Richards, Yan Li, Weiqun Shen, Benjamin Blair, Na Du, Kyndal Morais, Kate Lawrence, Lucy Lu, Chin I. Pai, Donghui Li, Mark Brunswick, Yanliang Zhang, Henry JiSlobodan Paessler, Robert D. Allen

Pathology

Research output: Contribution to journal › Article › peer-review

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 naïve 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.

Original language	English (US)
Journal	Unknown Journal
DOIs	https://doi.org/10.1101/2020.09.27.316174
State	Published - Sep 28 2020

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Immunology and Microbiology(all)
Neuroscience(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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Cao, X., Maruyama, J., Zhou, H., Kerwin, L., Sattler, R., Manning, J. T., Johnson, S., Richards, S., Li, Y., Shen, W., Blair, B., Du, N., Morais, K., Lawrence, K., Lu, L., Pai, C. I., Li, D., Brunswick, M., Zhang, Y., ... Allen, R. D. (2020). Discovery and development of human SARS-CoV-2 neutralizing antibodies using an unbiased phage display library approach. Unknown Journal. https://doi.org/10.1101/2020.09.27.316174

Discovery and development of human SARS-CoV-2 neutralizing antibodies using an unbiased phage display library approach. / Cao, Xia; Maruyama, Junki; Zhou, Heyue; Kerwin, Lisa; Sattler, Rachel; Manning, John T.; Johnson, Sachi; Richards, Susan; Li, Yan; Shen, Weiqun; Blair, Benjamin; Du, Na; Morais, Kyndal; Lawrence, Kate; Lu, Lucy; Pai, Chin I.; Li, Donghui; Brunswick, Mark; Zhang, Yanliang; Ji, Henry; Paessler, Slobodan; Allen, Robert D.

In: Unknown Journal, 28.09.2020.

Research output: Contribution to journal › Article › peer-review

Cao, X, Maruyama, J, Zhou, H, Kerwin, L, Sattler, R, Manning, JT, Johnson, S, Richards, S, Li, Y, Shen, W, Blair, B, Du, N, Morais, K, Lawrence, K, Lu, L, Pai, CI, Li, D, Brunswick, M, Zhang, Y, Ji, H, Paessler, S & Allen, RD 2020, 'Discovery and development of human SARS-CoV-2 neutralizing antibodies using an unbiased phage display library approach', Unknown Journal. https://doi.org/10.1101/2020.09.27.316174

Cao, Xia ; Maruyama, Junki ; Zhou, Heyue ; Kerwin, Lisa ; Sattler, Rachel ; Manning, John T. ; Johnson, Sachi ; Richards, Susan ; Li, Yan ; Shen, Weiqun ; Blair, Benjamin ; Du, Na ; Morais, Kyndal ; Lawrence, Kate ; Lu, Lucy ; Pai, Chin I. ; Li, Donghui ; Brunswick, Mark ; Zhang, Yanliang ; Ji, Henry ; Paessler, Slobodan ; Allen, Robert D. / Discovery and development of human SARS-CoV-2 neutralizing antibodies using an unbiased phage display library approach. In: Unknown Journal. 2020.

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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 na{\"i}ve 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.",

author = "Xia Cao and Junki Maruyama and Heyue Zhou and Lisa Kerwin and Rachel Sattler and Manning, {John T.} and Sachi Johnson and Susan Richards and Yan Li and Weiqun Shen and Benjamin Blair and Na Du and Kyndal Morais and Kate Lawrence and Lucy Lu and Pai, {Chin I.} and Donghui Li and Mark Brunswick and Yanliang Zhang and Henry Ji and Slobodan Paessler and Allen, {Robert D.}",

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AU - Ji, Henry

AU - Paessler, Slobodan

AU - Allen, Robert D.

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