The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients.

Lakshmanane Premkumar,Yara Park,Matthew H Collins,Erin M Scherer,Longping V Tse,Nadine Rouphael,Daniela Weiskopf,Caitlin E Edwards,Bruno Segovia-Chumbez,Ralph S Baric,Ramesh Jadi,Yixuan J Hou,Aravinda M De Silva,Alena J Markmann,David R Martinez,Srilatha Edupuganti,Alessandro Sette,Rajendra Raut,Caleb Cornaby,John L Schmitz ,Eric T Weimer ,Susan R Weiss ,Luther A Bartelt ,David M Margolis

doi:10.1126/sciimmunol.abc8413

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus can present with clinically inapparent, mild, or severe disease. Currently, the virus infection in individuals and at the population level is being monitored by PCR testing of symptomatic patients for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor binding domain (RBD) of the spike protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV-specific antibodies in people. Here we use a large panel of human sera (63 SARS-CoV-2 patients and 71 control subjects) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate RBD's performance as an antigen for reliable detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) for antibodies induced by SARS-CoVs. We observed a strong correlation between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-CoV-2 neutralizing antibodies in people.

Highlights

The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is responsible for an ongoing pandemic that has already killed over 320,000 people and paralyzed the global economy [1]
We used sera and monoclonal antibodies from animals immunized with SARS-CoV-1 or -2 spike proteins to assess the structural integrity of the purified recombinant receptor binding domain (RBD) antigens
These results suggest that the purified recombinant RBD antigens retain native structures required for specific antibody binding

Summary

Introduction

(SARS-CoV-2) is responsible for an ongoing pandemic that has already killed over 320,000 people and paralyzed the global economy [1]. There is an urgent need for highly specific and sensitive antibody detection assays to answer fundamental questions about the epidemiology and pathogenesis of SARSCoV-2 and to implement and evaluate population-level control programs [2]. Efforts to understand the pathogenesis and define risk factors for severe SARS-CoV-2 disease have been hampered by our inability to identify all infected individuals, irrespective of clinical symptoms. Many countries resorted to the widespread quarantine of cities and regions. By deploying reliable antibody assays for population-level testing, it will be possible to obtain the highresolution spatial data needed to implement policies for containing the epidemic and informing strategies for re-opening communities and cities

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Conclusion