LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection

Abstract

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.

A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19

“…In preclinical models of Covid-19, the use of LY-CoV555 improved clinical outcomes. 5 A dose of 7000 mg was chosen on the basis of pharmacokinetic and preliminary safety data.…”

“…To understand the possible role of neutralizing monoclonal antibodies and other antiviral interventions in patients who are hospitalized with Covid-19, the National Institutes of Health established the ACTIV-3/TICO (Therapeutics for Inpatients with Covid-19) platform 4 for the efficient conduct of trials. The first trial within the TICO platform was a comparison of LY-CoV555 5 and placebo. We report here the preliminary results of this trial.…”

Prophylaxis for COVID-19: a systematic review

“…Amongst the seven animal studies, four looked at the use of antibodies [ [21] , [22] , [23] , [24] ]. All found an effect although they did not report comparable outcomes.…”

“…All found an effect although they did not report comparable outcomes. Jones et al [ 21 ] reported reduced viral replication, Li et al and Tortorici et al reported high prophylactic efficacy [ 22 , 24 ], while rogers et al reported a 50% reduction in disease as measured by weight loss [ 25 ].The three remaining animal studies looked at the effect of HCQ alone [ 25 , 26 ] or compared to favipiravir [ 25 ]. All three demonstrated no observed effect of HCQ but Kaptein et al did show that favipiravir significantly reduced infectious titre [ 25 ].…”

CRISPR systems: Novel approaches for detection and combating COVID-19

“…Convalescent plasma is routinely used for patients with COVID-19 but recombinant antibodies need more in vitro and in vivo evaluation to investigate their prophylactic and therapeutic efficacy. Fascinatingly, LY-CoV555, a monoclonal antibody derived from a recovered COVID-19 patient (NCT004497987) ( Jones et al, 2020 ) and REGN-COV-2, a combination of two monoclonal antibodies targeting two regions of S protein (NCT04452318) ( Baum et al, 2020 ) are being progressed to phase 3 clinical trial ( Table 1 ).…”