LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection
| Autor: | Mark J. Mulligan, Kizzmekia S. Corbett, Marissa H. Piper, Nicole V. Johnson, Jory A. Goldsmith, Roza Bidshahri, Carl L. Hansen, Robert W. Cross, Daniel Wrapp, A. Pustilnik, Yuri Hwang, Julian Davies, Adil Mohamed, Kathryn Westendorf, Beverly A. Heinz, Olubukola M. Abiona, Lucas Kraft, Jamie L. Blackbourne, Andrew C. Adams, Marie I. Samanovic, Samuel J. Hinshaw, Bryan Edward Jones, Sean A. Tycho, Christopher M. Wiethoff, Shawn J. Berens, Krithika Muthuraman, Stefanie Zentelis, Thomas W. Geisbert, Richard E. Higgs, Ralph S. Baric, Lingshu Wang, Jorg Hendle, Maia A. Smith, Hayley M. Belli, Meike Dittmann, Deepa Balasubramaniam, Solmaz Sobhanifar, Rodrigo Goya, Denisa Foster, John R. Mascola, Viktoriya Borisevich, Thomas P. Cujec, Barney S. Graham, Ping Xiang, Jason S. McLellan, Davide Pellacani, David R. Martinez, Maren de Vries, Patricia Brown-Augsburger, Franz J. Triana, David Collins, Ester Falconer, Kevin R. Jepson, Bryan C. Barnhart, Ching-Lin Hsieh |
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| Rok vydání: | 2020 |
| Předmět: |
Coronavirus disease 2019 (COVID-19)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Medicine skin and connective tissue diseases Neutralizing antibody Research Articles biology business.industry fungi Antiviral antibody respiratory system biology.organism_classification Virology respiratory tract diseases STM r-articles body regions Coronavirus Rhesus macaque medicine.anatomical_structure Viral replication biology.protein Antibody business Research Article Respiratory tract |
| Zdroj: | Science Translational Medicine |
| DOI: | 10.1101/2020.09.30.318972 |
| Popis: | LY-CoV555, a SARS-CoV-2 spike protein–specific antibody, neutralizes SARS-CoV-2 and protects the airways of nonhuman primates against infection. A monoclonal for SARS-CoV-2 Among the most promising therapeutic options for individuals with coronavirus disease 2019 (COVID-19) are monoclonal antibodies (mAbs). In this study, Jones et al. identified, characterized, and tested one such mAb, LY-CoV555, in vitro and in vivo. They found that LY-CoV555 bound to the severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) spike protein and prevented its interaction with angiotensin-converting enzyme 2. Prophylactic treatment with LY-CoV555 protected the upper and lower respiratory tracts of nonhuman primates from becoming infected with SARS-CoV-2. Together, these data support the clinical use of LY-CoV555 for treating patients with COVID-19. 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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