We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates.
- Authors
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.
- Abstract
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.
- Subjects
SARS-CoV-2; COVID-19; VIRAL antibodies; HIGH throughput screening (Drug development); MONOCLONAL antibodies; KRA
- Publication
Science Translational Medicine, 2021, Vol 13, Issue 593, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.abf1906