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The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients.
Sci Immunol. 2020 06 11; 5(48)SI

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.

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Publisher Full Text
ncbi.nlm.nih.gov
immunology.sciencemag.org
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Authors+Show Affiliations

Premkumar L
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA prem@med.unc.edu aravinda_desilva@med.unc.edu.
Segovia-Chumbez B
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA.
Jadi R
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA.
Martinez DR
Department of Epidemiology, UNC Chapel Hill School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Raut R
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA.
Markmann A
Departments of Medicine, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA.
Cornaby C
Immunology/Histocompatibility and Immunogenetics Laboratories, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA.
Bartelt L
Departments of Medicine, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA.
Weiss S
Departments of Medicine, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA.
Park Y
Departments of Medicine, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA.
Edwards CE
Department of Epidemiology, UNC Chapel Hill School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Weimer E
Department of Pathology & Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA.
Scherer EM
Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Decatur, Georgia, USA.
Rouphael N
Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Decatur, Georgia, USA.
Edupuganti S
Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Decatur, Georgia, USA.
Weiskopf D
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
Tse LV
Department of Epidemiology, UNC Chapel Hill School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Hou YJ
Department of Epidemiology, UNC Chapel Hill School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Margolis D
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA. Department of Epidemiology, UNC Chapel Hill School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. Departments of Medicine, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA.
Sette A
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA. Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
Collins MH
Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Decatur, Georgia, USA.
Schmitz J
Department of Pathology & Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA.
Baric RS
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA. Department of Epidemiology, UNC Chapel Hill School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
de Silva AM
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill NC 27599, USA prem@med.unc.edu aravinda_desilva@med.unc.edu.

MeSH

AnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralBetacoronavirusCOVID-19Coronavirus InfectionsHumansImmunodominant EpitopesKineticsMiceMice, Inbred BALB CPandemicsPneumonia, ViralProtein BindingProtein DomainsRabbitsSARS VirusSARS-CoV-2Serologic TestsSpike Glycoprotein, CoronavirusZoonoses

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32527802

Citation

Premkumar, Lakshmanane, et al. "The Receptor Binding Domain of the Viral Spike Protein Is an Immunodominant and Highly Specific Target of Antibodies in SARS-CoV-2 Patients." Science Immunology, vol. 5, no. 48, 2020.
Premkumar L, Segovia-Chumbez B, Jadi R, et al. The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. Sci Immunol. 2020;5(48).
Premkumar, L., Segovia-Chumbez, B., Jadi, R., Martinez, D. R., Raut, R., Markmann, A., Cornaby, C., Bartelt, L., Weiss, S., Park, Y., Edwards, C. E., Weimer, E., Scherer, E. M., Rouphael, N., Edupuganti, S., Weiskopf, D., Tse, L. V., Hou, Y. J., Margolis, D., ... de Silva, A. M. (2020). The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. Science Immunology, 5(48). https://doi.org/10.1126/sciimmunol.abc8413
Premkumar L, et al. The Receptor Binding Domain of the Viral Spike Protein Is an Immunodominant and Highly Specific Target of Antibodies in SARS-CoV-2 Patients. Sci Immunol. 2020 06 11;5(48) PubMed PMID: 32527802.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. AU - Premkumar,Lakshmanane, AU - Segovia-Chumbez,Bruno, AU - Jadi,Ramesh, AU - Martinez,David R, AU - Raut,Rajendra, AU - Markmann,Alena, AU - Cornaby,Caleb, AU - Bartelt,Luther, AU - Weiss,Susan, AU - Park,Yara, AU - Edwards,Caitlin E, AU - Weimer,Eric, AU - Scherer,Erin M, AU - Rouphael,Nadine, AU - Edupuganti,Srilatha, AU - Weiskopf,Daniela, AU - Tse,Longping V, AU - Hou,Yixuan J, AU - Margolis,David, AU - Sette,Alessandro, AU - Collins,Matthew H, AU - Schmitz,John, AU - Baric,Ralph S, AU - de Silva,Aravinda M, PY - 2020/05/16/received PY - 2020/06/09/accepted PY - 2020/6/13/entrez PY - 2020/6/13/pubmed PY - 2020/6/27/medline JF - Science immunology JO - Sci Immunol VL - 5 IS - 48 N2 - 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. SN - 2470-9468 UR - https://www.unboundmedicine.com/medline/citation/32527802/The_receptor_binding_domain_of_the_viral_spike_protein_is_an_immunodominant_and_highly_specific_target_of_antibodies_in_SARS_CoV_2_patients_ L2 - https://immunology.sciencemag.org/cgi/pmidlookup?view=long&pmid=32527802 DB - PRIME DP - Unbound Medicine ER -