LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection

Jones, B. E.; Brown-Augsburger, P. L.; Corbett, K. S.; Westerndorf, K.; Davies, J.; Cujec, T. P.; Wiethoff, C. M.; Blackbourne, J. L.; Heinz, B. A.; Foster, D.; Higgs, R. E.; Balasubramaniam, D.; Wang, L.; Bidshahri, R.; Kraft, L.; Hwang, Y.; Zentelis, S.; Jepson, K. R.; Goya, R.; Smith, M. A.; Collins, D. W.; Hinshaw, S. J.; Tycho, S. A.; Pellacani, D.; Xiang, P.; Muthuraman, K.; Sobhanifar, S.; Piper, M. H.; Triana, F. J.; Hendle, J.; Pustilnik, A.; Adams, A. C.; Berens, S. J.; Baric, R. S.; Martinez, D. R.; Cross, R. W.; Geisbert, T. W.; Borisevich, V.; Abiona, O.; Belli, H. M.; de Vries, M

doi:10.1101/2020.09.30.318972

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bioRxiv · 10.1101/2020.09.30.318972

LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection

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Abstract

SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity. In a rhesus macaque challenge model, prophylaxis doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract. These data demonstrate that high-throughput screening can lead to the identification of a potent antiviral antibody that protects against SARS-CoV-2 infection. One Sentence SummaryLY-CoV555, an anti-spike antibody derived from a convalescent COVID-19 patient, potently neutralizes SARS-CoV-2 and protects the upper and lower airways of non-human primates against SARS-CoV-2 infection.

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Jones, B. E., Brown-Augsburger, P. L., Corbett, K. S., Westerndorf, K., Davies, J., Cujec, T. P., Wiethoff, C. M., Blackbourne, J. L., Heinz, B. A., Foster, D., Higgs, R. E., Balasubramaniam, D., Wang, L., Bidshahri, R., Kraft, L., Hwang, Y., Zentelis, S., Jepson, K. R., Goya, R., Smith, M. A., Collins, D. W., Hinshaw, S. J., Tycho, S. A., Pellacani, D., Xiang, P., Muthuraman, K., Sobhanifar, S., Piper, M. H., Triana, F. J., Hendle, J., Pustilnik, A., Adams, A. C., Berens, S. J., Baric, R. S., Martinez, D. R., Cross, R. W., Geisbert, T. W., Borisevich, V., Abiona, O., Belli, H. M., de Vries, M. 2020-10-01. LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection. https://doi.org/10.1101/2020.09.30.318972

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