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

Publication ,  Journal Article
Jones, BE; Brown-Augsburger, PL; Corbett, KS; Westendorf, K; Davies, J; Cujec, TP; Wiethoff, CM; Blackbourne, JL; Heinz, BA; Foster, D; Wang, L ...
Published in: Sci Transl Med
May 12, 2021

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.

Duke Scholars

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

May 12, 2021

Volume

13

Issue

593

Location

United States

Related Subject Headings

  • Spike Glycoprotein, Coronavirus
  • SARS-CoV-2
  • Macaca mulatta
  • COVID-19
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • Animals
  • 4003 Biomedical engineering
  • 3206 Medical biotechnology
  • 11 Medical and Health Sciences
 

Citation

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Jones, B. E., Brown-Augsburger, P. L., Corbett, K. S., Westendorf, K., Davies, J., Cujec, T. P., … Falconer, E. (2021). The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci Transl Med, 13(593). https://doi.org/10.1126/scitranslmed.abf1906
Jones, Bryan E., Patricia L. Brown-Augsburger, Kizzmekia S. Corbett, Kathryn Westendorf, Julian Davies, Thomas P. Cujec, Christopher M. Wiethoff, et al. “The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates.Sci Transl Med 13, no. 593 (May 12, 2021). https://doi.org/10.1126/scitranslmed.abf1906.
Jones BE, Brown-Augsburger PL, Corbett KS, Westendorf K, Davies J, Cujec TP, et al. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci Transl Med. 2021 May 12;13(593).
Jones, Bryan E., et al. “The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates.Sci Transl Med, vol. 13, no. 593, May 2021. Pubmed, doi:10.1126/scitranslmed.abf1906.
Jones BE, Brown-Augsburger PL, Corbett KS, Westendorf K, Davies J, Cujec TP, Wiethoff CM, Blackbourne JL, Heinz BA, Foster D, Higgs RE, Balasubramaniam D, Wang L, Zhang Y, Yang ES, Bidshahri R, Kraft L, Hwang Y, Žentelis S, Jepson KR, Goya R, Smith MA, Collins DW, Hinshaw SJ, Tycho SA, Pellacani D, Xiang P, Muthuraman K, Sobhanifar S, Piper MH, Triana FJ, Hendle J, Pustilnik A, Adams AC, Berens SJ, Baric RS, Martinez DR, Cross RW, Geisbert TW, Borisevich V, Abiona O, Belli HM, de Vries M, Mohamed A, Dittmann M, Samanovic MI, Mulligan MJ, Goldsmith JA, Hsieh C-L, Johnson NV, Wrapp D, McLellan JS, Barnhart BC, Graham BS, Mascola JR, Hansen CL, Falconer E. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci Transl Med. 2021 May 12;13(593).

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

May 12, 2021

Volume

13

Issue

593

Location

United States

Related Subject Headings

  • Spike Glycoprotein, Coronavirus
  • SARS-CoV-2
  • Macaca mulatta
  • COVID-19
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • Animals
  • 4003 Biomedical engineering
  • 3206 Medical biotechnology
  • 11 Medical and Health Sciences