A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization

Autor: P Neubert, Matthias Vogel, Viola Hähnel, Matthias Lubnow, Thomas Glück, Vivian Glück, Mara Kiessling, Maren Werner, Ralph Burkhardt, Bernd Salzberger, Franz Audebert, André Gessner, Dirk Lunz, Maria Deichner, Jürgen J. Wenzel, Stefanie Frisch, S Schmid, Frank Hanses, Veruschka Albert, Philipp Schuster, Hans Helmut Niller, Ralf Wagner, Nicole Ritter, Martina Müller, Thomas Müller, Barbara Schmidt, Leon Babl, Michael Koller, Philip Pervan, Florian Hitzenbichler, Robert Offner, Jonathan Jantsch, David Peterhoff, Anja Schütz, Bernhard M. Graf
Rok vydání: 2020
Předmět:
0301 basic medicine
viruses
Assay validation
610 Medizin
Antibodies
Viral
medicine.disease_cause
Neutralization
Antigens
Viral
Coronavirus
ddc:610
biology
General Medicine
Virus neutralization
SARS-CoV-2 · COVID-19 · Antibody test · ELISA · Serology · Virus neutralization · Assay validation · Spike protein · S protein · Receptor binding domain
Vaccination
Serology
Infectious Diseases
Ectodomain
Antibody test
Spike Glycoprotein
Coronavirus
ELISA
Antibody
Microbiology (medical)
030106 microbiology
Enzyme-Linked Immunosorbent Assay
Spike protein
Sensitivity and Specificity
S protein
03 medical and health sciences
Protein Domains
Antigen
Neutralization Tests
medicine
Humans
Seroprevalence
Seroconversion
Original Paper
SARS-CoV-2
business.industry
Immune Sera
COVID-19
Antibodies
Neutralizing
Virology
Immunoglobulin A
Cross-Sectional Studies
030104 developmental biology
Immunoglobulin M
Immunoglobulin G
biology.protein
business
Receptor binding domain
Zdroj: Infection
ISSN: 1439-0973
0300-8126
DOI: 10.1007/s15010-020-01503-7
Popis: ObjectiveThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic challenges national health systems and the global economy. Monitoring of infection rates and seroprevalence can guide public health measures to combat the pandemic. This depends on reliable tests on active and former infections. Here, we set out to develop and validate a specific and sensitive enzyme linked immunosorbent assay (ELISA) for detection of anti-SARS-CoV-2 antibody levels.MethodsIn our ELISA, we used SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike (S) ectodomain as antigens. We assessed sera from patients infected with seasonal coronaviruses, SARS-CoV-2 and controls. We determined and monitored IgM-, IgA- and IgG-antibody responses towards these antigens. In addition, for a panel of 22 sera, virus neutralization and ELISA parameters were measured and correlated.ResultsThe RBD-based ELISA detected SARS-CoV-2-directed antibodies, did not cross-react with seasonal coronavirus antibodies and correlated with virus neutralization (R2 = 0.89). Seroconversion started at 5 days after symptom onset and led to robust antibody levels at 10 days after symptom onset. We demonstrate high specificity (99.3%;N = 1000) and sensitivity (92% for IgA, 96% for IgG and 98% for IgM; > 10 days after PCR-proven infection;N = 53) in serum.ConclusionsWith the described RBD-based ELISA protocol, we provide a reliable test for seroepidemiological surveys. Due to high specificity and strong correlation with virus neutralization, the RBD ELISA holds great potential to become a preferred tool to assess thresholds of protective immunity after infection and vaccination.
Databáze: OpenAIRE
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