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

Bryan E. Jones(Eli Lilly (United States)), Patricia Brown‐Augsburger(Eli Lilly (United States)), Kizzmekia S. Corbett(National Institutes of Health), Kathryn Westendorf(AbCellera (Canada)), Julian Davies(Eli Lilly (United States)), Thomas P. Cujec(Eli Lilly (United States)), Christopher M. Wiethoff(Eli Lilly (United States)), Jamie L. Blackbourne(Eli Lilly (United States)), Beverly A. Heinz(Eli Lilly (United States)), Denisa Foster(Eli Lilly (United States)), Richard E. Higgs(Eli Lilly (United States)), Deepa Balasubramaniam(Eli Lilly (United States)), Lingshu Wang(National Institutes of Health), Roza Bidshahri(AbCellera (Canada)), Lucas Kraft(AbCellera (Canada)), Yuri Hwang(AbCellera (Canada)), Stefanie Žentelis(AbCellera (Canada)), Kevin R. Jepson(AbCellera (Canada)), Rodrigo Goya(AbCellera (Canada)), Maia A. Smith(AbCellera (Canada)), David W. Collins(AbCellera (Canada)), Samuel J. Hinshaw(AbCellera (Canada)), Sean A. Tycho(AbCellera (Canada)), Davide Pellacani(AbCellera (Canada)), Ping Xiang(AbCellera (Canada)), Krithika Muthuraman(AbCellera (Canada)), Solmaz Sobhanifar(AbCellera (Canada)), Marissa H. Piper(Eli Lilly (United States)), Franz J. Triana(Eli Lilly (United States)), J. Hendle(Eli Lilly (United States)), Anna Pustilnik(Eli Lilly (United States)), Andrew C. Adams(Eli Lilly (United States)), Shawn Berens(Eli Lilly (United States)), Ralph S. Baric(University of North Carolina at Chapel Hill), David R. Martinez(University of North Carolina at Chapel Hill), Robert W. Cross(The University of Texas Medical Branch at Galveston), Thomas W. Geisbert(The University of Texas Medical Branch at Galveston), Viktoriya Borisevich(The University of Texas Medical Branch at Galveston), Olubukola M. Abiona(National Institutes of Health), Hayley M. Belli(New York University), Maren de Vries(New York University), Adil Mohamed(New York University), Meike Dittmann(New York University), Marie I. Samanovic(New York University), Mark J. Mulligan(New York University), Jory A. Goldsmith(The University of Texas at Austin), Ching‐Lin Hsieh(The University of Texas at Austin), Nicole V. Johnson(The University of Texas at Austin), Daniel Wrapp(The University of Texas at Austin), Jason S. McLellan(The University of Texas at Austin), Bryan C. Barnhart(AbCellera (Canada)), Barney S. Graham(National Institutes of Health), John R. Mascola(National Institutes of Health), Carl L. Hansen(AbCellera (Canada)), Ester Falconer(AbCellera (Canada))
bioRxiv (Cold Spring Harbor Laboratory)
October 1, 2020
Cited by 175Open Access
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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 SUMMARY: LY-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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