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The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates

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 popula...

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Detalles Bibliográficos
Autores principales: Jones, Bryan E., Brown-Augsburger, Patricia L., Corbett, Kizzmekia S., Westendorf, Kathryn, Davies, Julian, Cujec, Thomas P., Wiethoff, Christopher M., Blackbourne, Jamie L., Heinz, Beverly A., Foster, Denisa, Higgs, Richard E., Balasubramaniam, Deepa, Wang, Lingshu, Zhang, Yi, Yang, Eun Sung, Bidshahri, Roza, Kraft, Lucas, Hwang, Yuri, Žentelis, Stefanie, Jepson, Kevin R., Goya, Rodrigo, Smith, Maia A., Collins, David W., Hinshaw, Samuel J., Tycho, Sean A., Pellacani, Davide, Xiang, Ping, Muthuraman, Krithika, Sobhanifar, Solmaz, Piper, Marissa H., Triana, Franz J., Hendle, Jorg, Pustilnik, Anna, Adams, Andrew C., Berens, Shawn J., Baric, Ralph S., Martinez, David R., Cross, Robert W., Geisbert, Thomas W., Borisevich, Viktoriya, Abiona, Olubukola, Belli, Hayley M., de Vries, Maren, Mohamed, Adil, Dittmann, Meike, Samanovic, Marie I., Mulligan, Mark J., Goldsmith, Jory A., Hsieh, Ching-Lin, Johnson, Nicole V., Wrapp, Daniel, McLellan, Jason S., Barnhart, Bryan C., Graham, Barney S., Mascola, John R., Hansen, Carl L., Falconer, Ester
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284311/
https://www.ncbi.nlm.nih.gov/pubmed/33820835
http://dx.doi.org/10.1126/scitranslmed.abf1906
Descripción
Sumario: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.