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

TLDR

SARS‑CoV‑2, emerging in late 2019, causes a pandemic of respiratory illness ranging from asymptomatic to severe disease, and current surveillance relies on PCR testing of symptomatic patients while the spike protein’s receptor‑binding domain, poorly conserved among coronaviruses, offers a promising target for specific antibody detection. There is an urgent need for serologic tests to identify all infected individuals, irrespective of symptoms, to conduct surveillance and contain spread. Here we used a large panel of human sera (63 SARS‑CoV‑2 patients and 71 controls) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate the performance of recombinant RBD as an antigen for reliable detection of SARS‑CoV‑2‑specific antibodies. By day 9 after symptom onset, recombinant RBD antigen detected SARS‑CoV‑2 antibodies with 98 % sensitivity and 100 % specificity, and antibody levels correlated strongly with neutralizing activity, supporting its use in serologic diagnostics and as a correlate of neutralization.

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.