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

By Bryan E. Jones, Patricia L. Brown-Augsburger, Kizzmekia S. Corbett, Kathryn Westendorf, Julian Davies, Thomas P. Cujec, Christopher M. Wiethoff, Jamie L. Blackbourne, Beverly A. Heinz, Denisa Foster, Richard E. Higgs, Deepa Balasubramaniam, Lingshu Wang, Roza Bidshahri, Lucas Kraft, Yuri Hwang, Stefanie Žentelis, Kevin R. Jepson, Rodrigo Goya, Maia A. Smith, David W Collins, Samuel J. Hinshaw, Sean A. Tycho, Davide Pellacani, Ping Xiang, Krithika Muthuraman, Solmaz Sobhanifar, Marissa H. Piper, Franz J. Triana, Jorg Hendle, Anna Pustilnik, Andrew C. Adams, Shawn J. Berens, Ralph S. Baric, David R. Martinez, Robert W Cross, Thomas W Geisbert, Viktoriya Borisevich, Olubukola Abiona, Hayley M. Belli, Maren de Vries, Adil Mohamed, Meike Dittmann, Marie I Samanovic, Mark J Mulligan, Jory A Goldsmith, Ching-Lin Hsieh, Nicole V Johnson, Daniel Wrapp, Jason S McLellan, Bryan C. Barnhart, Barney S. Graham, John R Mascola, Carl L. Hansen, Ester Falconer

Posted 01 Oct 2020
bioRxiv DOI: 10.1101/2020.09.30.318972 (published DOI: 10.1126/scitranslmed.abf1906)

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. ### Competing Interest Statement M.J.M. has research grant funding from NIH/NIAID, Pfizer, and Sanofi; and personal fees from Meissa Vaccines, Inc. B.E.J., P.LB., J.D., T.P.C., C.M.W., J.L.B., B.A.H., R.E.H., D.B., D.F., M.H.P., F.J.T., J.H., A.P., A.C.A. and S.J.B. are employees and stockholders of Eli Lilly and Company. K.W., R.B., L.K., S.J.H., S.S., B.C.B, and E.F. are employees of AbCellera Biologics Inc. C.L.H., R.G., D.P., P.X., Y.H., R.B., K.R.J. M.A.S., S.Z., D.W.C., and S.A.T. are employees and stockholders of AbCellera Biologics Inc.. K.M. is a former employee and stockholder of AbCellera Biologics Inc. M.D. received a contract from Eli Lilly and Company to support the studies reported herein. Authors from AbCellera Biologics Inc., National Institute of Allergy and Infectious Diseases (K.S.C., B.S.G., and J.R.M.), and Eli Lilly and Company are inventors on patent applications related to the work described here. R.S.B., D.R.M., R.W.C., T.W.G, V.B., O.A., L.W., H.M.B., M.D.V., A.D., M.S., J.A.G., C.L.H., N.V.J., J.S.M., and D.W. declare no competing interests.

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