ABSTRACT
LY-CoV1404 is a highly potent, neutralizing, SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody identified from a convalescent COVID-19 patient approximately 60 days after symptom onset. In pseudovirus studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1.1.7, B.1.351, B.1.427/B.1.429, P.1, and B.1.526 and binds to these variants in the presence of their underlying RBD mutations (which include K417N, L452R, E484K, and N501Y). LY-CoV1404 also neutralizes authentic SARS-CoV-2 in two different assays against multiple isolates. The RBD positions comprising the LY-CoV1404 epitope are highly conserved, with the exception of N439 and N501; notably the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The breadth of variant binding, potent neutralizing activity and the relatively conserved epitope suggest that LY-CoV1404 is one in a panel of well-characterized, clinically developable antibodies that could be deployed rapidly to address current and emerging variants. New variant-resistant treatments such as LY-CoV1404 are desperately needed, given that some of the existing therapeutic antibodies are less effective or ineffective against certain variants and the impact of variants on vaccine efficacy is still poorly understood.
Subject(s)
COVID-19ABSTRACT
SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity. In a rhesus macaque challenge model, prophylaxis doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract. These data demonstrate that high-throughput screening can lead to the identification of a potent antiviral antibody that protects against SARS-CoV-2 infection.