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Spike antibody specificity
Serology testing that accurately detects antibodies to the SARS-CoV-2 coronavirus is a foundational tool needed to select appropriate measures to control the COVID-19 pandemic and assess the performance of candidate human vaccines. Premkumar et al. used the receptor-binding domain (RBD) portion of the SARS-CoV-2 spike protein to develop an immunoassay that detects RBD-binding antibodies in serum with high sensitivity and specificity by 9 days after onset of patient symptoms. They found that the presence of RBD-binding antibodies correlated strongly with the emergence of neutralizing antibodies. Antibodies to the RBDs of human common cold coronaviruses were present in most adults but did not cross-react with the SARS-CoV-2 RBD. These findings pave the way for expanded use of RBD-based serology tests to broadly assess humoral immunity to SARS-CoV-2.
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.
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