The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates
| Autor: | Krithika Muthuraman, Richard E. Higgs, Carl L. Hansen, Maren de Vries, Mark J. Mulligan, Kizzmekia S. Corbett, Ping Xiang, Nicole V. Johnson, Jory A. Goldsmith, Jason S. McLellan, John R. Mascola, Marissa H. Piper, Lucas Kraft, Jamie L. Blackbourne, Samuel J. Hinshaw, Davide Pellacani, Stefanie Žentelis, Christopher M. Wiethoff, Solmaz Sobhanifar, David R. Martinez, Franz J. Triana, Thomas P. Cujec, Barney S. Graham, Robert W. Cross, Ching-Lin Hsieh, Beverly A. Heinz, Denisa Foster, Ralph S. Baric, Sean A. Tycho, Jorg Hendle, David Collins, Eun Sung Yang, Ester Falconer, Daniel Wrapp, Andrew C. Adams, Roza Bidshahri, A. Pustilnik, Yuri Hwang, Adil Mohamed, Julian Davies, Yi Zhang, Patricia Brown-Augsburger, Bryan Edward Jones, Shawn J. Berens, Kevin R. Jepson, Bryan C. Barnhart, Kathryn Westendorf, Lingshu Wang, Viktoriya Borisevich, Meike Dittmann, Maia A. Smith, Deepa Balasubramaniam, Thomas W. Geisbert, Rodrigo Goya, Hayley M. Belli, Olubukola M. Abiona, Marie I. Samanovic |
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| Rok vydání: | 2020 |
| Předmět: |
Antibodies
Viral Article 03 medical and health sciences 0302 clinical medicine Pharmacokinetics medicine Animals Respiratory system Neutralizing antibody 030304 developmental biology 0303 health sciences biology business.industry SARS-CoV-2 COVID-19 General Medicine biology.organism_classification Virology Antibodies Neutralizing Macaca mulatta 3. Good health Vaccination Rhesus macaque medicine.anatomical_structure Viral replication 030220 oncology & carcinogenesis Spike Glycoprotein Coronavirus biology.protein Antibody business Respiratory tract |
| Zdroj: | bioRxiv Science Translational Medicine |
| ISSN: | 1946-6242 |
| Popis: | Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. Here, we report that high-throughput microfluidic screening of antigen-specific B cells led to the identification of LY-CoV555 (also known as bamlanivimab), a potent anti-spike neutralizing antibody from a hospitalized, convalescent patient with coronavirus disease 2019 (COVID-19). Biochemical, structural, and functional characterization of LY-CoV555 revealed high-affinity binding to the receptor-binding domain, angiotensin-converting enzyme 2 binding inhibition, and potent neutralizing activity. A pharmacokinetic study of LY-CoV555 conducted in cynomolgus monkeys demonstrated a mean half-life of 13 days and a clearance of 0.22 ml hour-1 kg-1, consistent with a typical human therapeutic antibody. In a rhesus macaque challenge model, prophylactic doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract in samples collected through study day 6 after viral inoculation. This antibody has entered clinical testing and is being evaluated across a spectrum of COVID-19 indications, including prevention and treatment. |
| Databáze: | OpenAIRE |
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