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

• Type of Material: Article
• Authors: Lakshmanane Premkumar, University of North Carolina; Bruno Segovia-Chumbez, University of North Carolina; Ramesh Jadi, University of North Carolina; David R. Martinez, University of North Carolina; Rajendra Raut, University of North Carolina; Alena Markmann, University of North Carolina; Caleb Cornaby, University of North Carolina; Luther Bartelt, University of North Carolina; Susan Weiss, University of North Carolina; Yara Park, University of North Carolina; Caitlin E. Edwards, University of North Carolina; Eric Weimer, University of North Carolina; Erin Scherer, Emory University; Nadine Rouphael, Emory University; Srilatha Edupuganti, Emory University; Daniela Weiskopf, La Jolla Institute for Allergy and Immunology; Longping V. Tse, University of North Carolina; Yixuan J. Hou, University of North Carolina; David Margolis, University of North Carolina; Alessandro Sette, La Jolla Institute for Allergy and Immunology; Matthew Collins, Emory University; John Schmitz, University of North Carolina; Ralph S. Baric, University of North Carolina; Aravinda M. de Silva, University of North Carolina
• Language: English
• Date: 2020-06-01
• Publisher: American Association for the Advancement of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1126/sciimmunol.abc8413
• Title of Journal or Parent Work: Science Immunology
• Volume: 5
• Issue: 48
• Grant/Funding Information: NIH NIAID T32 AI007151 (D.M.); National Institutes of Health Contract 75N9301900065 (A.S. and D.W.); Burroughs Wellcome Fund Postdoctoral Enrichment Program Award (D.M.).; This work was funded by the University of North Carolina School of Medicine (L.P. and A.D.)
• Keywords: Reverse genetics; Life Sciences & Biomedicine; Immunology; Length infectious CDNA; Serological assays; SARS-COV; Syndrome associated coronavirus; Science & Technology
• Research Categories: Health Sciences, Pathology; Health Sciences, Public Health; Biology, Microbiology; Health Sciences, Immunology

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 polymerase chain reaction (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 individuals) 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.