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

By L. Premkumar, Bruno Segovia-Chumbez, R. Jadi, David R. Martinez, R. Raut, A. Markmann, Caleb Cornaby, L. Bartelt, S. Weiss, Yara Park and 14 more. Science immunology, 2020

843 citations recorded by the source corpus.

The serum level of RBD-binding antibodies correlates with SARS-CoV-2 neutralization and can be used for population-level surveillance. 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.

Subfields: Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/03f38b7239e4ae8f8bb7970b6b05eebd46038157

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In Infectious Diseases

1. D. Veesler
2. A. Walls
3. M. A. Tortorici
4. Alessandro Sette
5. Shane Crotty
6. Ralph S. Baric
7. Jesse D. Bloom

Citations in the corpus

• Adaptive immunity to SARS-CoV-2 and COVID-19 (2021, positive): “Antibodies and B cells The vast majority of SARS-CoV-2 infected individuals seroconvert within 5–15 days PSO, with 90% seroconversion by day 10 PSO (Long et al., 2020; Rydyznski Moderbacher et al., 2020; Premkumar et al., 2020; Ripperger et al., 2020; Suthar et al., 2020).”
• Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding (2020, positive): “Mutational constraint of antibody epitopes The RBD is the dominant target of neutralizing antibodies to SARS-CoV-2 (Brouwer et al., 2020; Cao et al., 2020; Ju et al., 2020; Premkumar et al., 2020; Rogers et al., 2020; Suthar et al., 2020; Yuan et al., 2020a; Zhang et al., 2020; Zost et al., 2020).”
• Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies (2020, positive): “S construction though we could not resolve densities for bound Fabs in the V107-S nsEMPEM reconstruction (Figure 4A), RBD-binding Cell 182, 828–842, August 20, 2020 833 (A) Reconstructed volumes for mAb C105 bound to SARS-CoV-2 S trimers in state 1 (two ‘‘up’’ RBDs, two bound Fabs) and state 2 (thre”
• Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity (2020, positive): “This RBD sequence is 346 amino acids in length, corresponding to amino acids 319-591 of the Spike protein sequences in the Protein Data Bank (PDB) deposited by Premkumar et al., 2020 (PDB 6VSB) and for the reference strain Wuhan-Hu-1 (PDB 6XR8).”
• Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19 (2020, positive): “This probe contains a very small fraction of all the potential antibody epitopes in SARSCoV-2 but is highly specific for this particular virus (Premkumar et al., 2020).”
• Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding (2020, neutral): “Mutational Constraint of Antibody Epitopes The RBD is the dominant target of neutralizing antibodies to SARS-CoV-2 (Brouwer et al., 2020; Cao et al., 2020; Ju et al., 2020; Pinto et al., 2020; Premkumar et al., 2020; Rogers et al., 2020; Suthar et al., 2020; Yuan et al., 2020a; Zhang et al., 2020; Z”