A Potent SARS-CoV-2 Neutralizing Human Monoclonal Antibody That Reduces Viral Burden and Disease Severity in Syrian Hamsters.

Rachel Adams,Ronald B Tjalkens,Miles Eckley,Emily Mount,Xiaomin Fan,Savannah M Rocha,Catherine Woods,Dilip Challa,Christine Tumanut,Wuxiang Liao,Karina Kuo,Adam Corper,Juliette Lewis,Lin Li,Tony Schountz,John Manhard,Anna C Fagre,Shijun Zhan,Tawfik Aboellail

doi:10.3389/fimmu.2020.614256

Rachel Adams, Ronald B Tjalkens + Show 17 more

Open Access

https://doi.org/10.3389/fimmu.2020.614256

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Abstract

The emergence of COVID-19 has led to a pandemic that has caused millions of cases of disease, variable morbidity and hundreds of thousands of deaths. Currently, only remdesivir and dexamethasone have demonstrated limited efficacy, only slightly reducing disease burden, thus novel approaches for clinical management of COVID-19 are needed. We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virus in vitro. Administration of the lead antibody clone to Syrian hamsters challenged with SARS-CoV-2 significantly reduced viral load and histopathology score in the lungs. Moreover, the antibody interrupted monocyte infiltration into the lungs, which may have contributed to the reduction of disease severity by limiting immunopathological exacerbation. The use of this antibody could provide an important therapy for treatment of COVID-19 patients.

Highlights

The emergence of a novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in December 2019 in Wuhan, China [1]
We describe an anti-SARS-CoV-2 spike RBD clone isolated from a rationally designed, fully human antibody library that bound to native spike protein
A rationally designed fully human antibody library displayed on yeast was screened by magnetic bead sorting (MACS) followed by two rounds of fluorescence activated cell sorting (FACS) using recombinant SARS-CoV-2 RBD (Arg319-Asn532 with a His-tag and Avi-tag at the C-terminus; Kactus BioSystems, Cat# COVVM4BDB) as antigen to enrich for yeast clones expressing antibody clones that bound the RBD antigen

Summary

Introduction

The emergence of a novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first described in December 2019 in Wuhan, China [1]. In a vulnerable subset of patients, the disease often progresses to an atypical pneumonia with high morbidity and mortality rates [2,3,4,5,6]. Mortality based on case fatality rates have ranged from early estimates of 3.9% in Hubei province, China, to 0.9% in populations from countries with widespread testing. Recent estimates of infection fatality rates (IFRs) are between 0.6 to 1% and overall indicate that COVID-19 has a 10-fold greater mortality. The effect on healthcare resources is of major concern and there is an increasingly unmet medical need for effective therapies, for older patients with comorbidities, including atherosclerosis, hypertension and diabetes mellitus, to prevent lethal pneumonia

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