New Antibody Test for COVID-19 Targets Unique Region of Spike Protein

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Scientists at the UNC School of Medicine have developed a new COVID-19 antibody test that includes a simplified experimental assay that could be ramped up to test thousands of blood samples at labs that do not have the resources of commercial labs and large academic medical centers.

The work is published in Science Immunology in the paper, “The receptor-binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients.”

The antibody test is based on the receptor-binding domain (RBD) of the spike protein. The RBD-based antibody test measures the levels of that domain, which the authors found correlate to the levels of neutralizing antibodies.

The RBD of the spike protein in SARS-CoV-2 is not shared among other known human or animal coronaviruses. Therefore, antibodies against this domain are likely to be highly specific to SARS-CoV-2, and so these antibodies reveal if an individual has been exposed to the virus that can cause COVID-19.

Given that, it “represents a promising antigen for detecting CoV-specific antibodies in people.”

Indeed, when the researchers tested blood collected from people exposed to other coronaviruses, none had antibodies to the RBD of SARS-CoV-2.

They used 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.

“Our assay is extremely specific for antibodies to the virus that causes COVID-19, which is not the case for some currently available antibody tests,” said co-senior author Aravinda de Silva, PhD, professor of microbiology and immunology at UNC. “Our results strongly support the use of RBD-based antibody assays for population-level surveillance and as a correlate of the neutralizing antibody levels in people who have recovered from SARS-CoV-2 infections.”

By day 9 after the onset of symptoms, the authors wrote that “the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) for antibodies induced by SARS-CoVs.” They noted that they observed a strong correlation “between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients.”

Their results, they wrote, 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.”

First author Prem Lakshmanane, PhD, assistant professor of microbiology and immunology at UNC, said, “We are now further streamlining our test into an inexpensive assay, so that instead of the test taking four to five hours to complete, our assay could be completed in about 70 minutes without compromising quality.”

The de Silva Lab collaborated with David Martinez, PhD, in the laboratory of world-renowned coronavirus expert Ralph Baric, PhD, to test if the RBD-based antibody levels in patients correlated with levels of neutralizing antibodies found in a similar assay developed in the Baric lab.

“We observed a robust correlation between levels of RBD-binding antibodies and SARS-CoV-2 neutralizing antibodies in individual samples,” Lakshmanane said. “This means our assay not only identifies people exposed to SARS-CoV-2, but it can also be used to predict levels of neutralizing antibodies and to identify potential donors for plasma therapy.”

“We don’t see our research as a means to replace commercial tests,” said de Silva. “Commercial tests are critical, especially for making decisions about the clinical management of individual patients. But it’s too early in the pandemic to know if the commercial assays are suitable for identifying people who experienced very mild or no disease after infection or if the assays tell us anything about protective immunity, as researchers are still learning about this virus.”

He added, “It’s important for researchers to stay engaged, to monitor antibody responses and other biological details, and to fine-tune assays to meet the different needs of individual patients, the public health community, and vaccine developers.”

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