7KMG

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

Jones, B.E., Brown-Augsburger, P.L., Corbett, K.S., Westendorf, K., Davies, J., Cujec, T.P., Wiethoff, C.M., Blackbourne, J.L., Heinz, B.A., Foster, D., Higgs, R.E., Balasubramaniam, D., Wang, L., Zhang, Y., Yang, E.S., Bidshahri, R., Kraft, L., Hwang, Y., Zentelis, S., Jepson, K.R., Goya, R., Smith, M.A., Collins, D.W., Hinshaw, S.J., Tycho, S.A., Pellacani, D., Xiang, P., Muthuraman, K., Sobhanifar, S., Piper, M.H., Triana, F.J., Hendle, J., Pustilnik, A., Adams, A.C., Berens, S.J., Baric, R.S., Martinez, D.R., Cross, R.W., Geisbert, T.W., Borisevich, V., Abiona, O., Belli, H.M., de Vries, M., Mohamed, A., Dittmann, M., Samanovic, M.I., Mulligan, M.J., Goldsmith, J.A., Hsieh, C.L., Johnson, N.V., Wrapp, D., McLellan, J.S., Barnhart, B.C., Graham, B.S., Mascola, J.R., Hansen, C.L., Falconer, E.

(2021) Sci Transl Med 13

• PubMed: 33820835 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1126/scitranslmed.abf1906
• Primary Citation of Related Structures:  
  7KMG, 7KMH, 7KMI


• PubMed Abstract: 
  

  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.

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Organizational Affiliation: 

Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA. [email protected] [email protected].