Developmental Biology - COVID19 Antibody Testing|
A New Type of COVID-19 Antibody Testing
A new test from the University of North Carolina Chapel Hill pinpoints human antibodies to the SARS-CoV-2 spike protein...
UNC-Chapel Hill scientists' have created a test specific to human antibodies in a unique part of the SARS-CoV-2 spike protein. The test can help document COVID-19 infections, even identify asymptomatic virus infection, while measuring the level of immunity in that individual.
As the COVID-19 pandemic continues with many thousands of new infections each day, there is a need for wide surveillance testing.
We need a better understanding of our infection rates, especially in people with mild or no symptoms, who can still be carriers.
UNC School of Medicine scientists along with their colleagues, have developed a new kind of antibody test. The test is a simplified assay. It can be ramped up to test thousands of blood samples without needing the resources of commercial labs or large academic medical centers.
The work, published in Science Immunology, uses a blood sample to pinpoint SARS-CoV-2 antibodies - targeting one unique piece of the SARS-CoV-2 spike protein.
That unique piece of SARS-CoV-2 protein is called a receptor binding domain, or RBD. This RBD based antibody test measures levels of that domain which correlate to the levels of the all-important neutralizing antibodies that provide immunity.
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. So these antibodies reveal if an individual has been exposed to the virus that can cause COVID-19.
Indeed, when researchers tested blood collected from people exposed to other coronaviruses, none had antibodies to the RBD of SARS-CoV-2.
"Our assay is extremely specific for antibodies to the virus causing COVID-19 — which is not the case for some currently available antibody tests.
Our results strongly support RBD-based antibody assays for population-level surveillance and correlate the neutralizing antibody levels in people who have recovered from SARS-CoV-2 infections."
Aravinda de Silva PhD, Professor, Microbiology and Immunology, UNC Institute for Global Health and Infectious Diseases.
"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."
Prem Lakshmanane PhD, Assistant Professor, Microbiology and Iimmunology, UNC.
During the UNC-Chapel Hill campus shutdown, Lakshmanane led a team of researchers including Ramesh Radi PhD, Bruno Segovia-Chumbez, and Rajendra Raut PhD - each designated as an emergency employee - to develop the test from scratch. The team designed new antigens and used a large panel of SARS-CoV-2 patients and control human and animal samples.
From day nine after the onset of symptoms and thereafter, the UNC assay allowed researchers to accurately identify RBD-based antibodies to SARS-CoV-2. World-renowned coronavirus expert Ralph Baric PhD, Kenan Distinguished Professor of Epidemiology at the UNC Gillings School of Global Public Health, developed an assay to measure neutralizing antibodies in these clinical samples.
Assays for measuring neutralizing antibodies take about three days to complete and often require special high-containment facilities for safely working with infectious viruses.
"We observed a robust correlation between levels of RBD-binding antibodies and SARS-CoV-2 neutralizing antibodies in individual samples. 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."
Prem Lakshmanane PhD
UNC-Chapel Hill researchers have received requests from scientists across the country and around the world for assistance with establishing this new assay within their research laboratories to monitor people for SARS-CoV-2 infection.
"We don't see our research as a means to replace commercial tests. 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.
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.
It's also 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."
Aravinda de Silva PhD
Authors are Bruno Segovia-Chumbez, Ramesh Jadi, David R. Martinez, Rajendra Raut, Alena Markmann, Caleb Cornaby, Luther Bartelt, Susan Weiss, Yara Park, Caitlin E. Edward, Eric Weimer, Erin M. Scherer, Nadine Roupael, Sri Edupuganti, Daniela Weiskopf, Longping V. Tse, Y. Jacob Hou, David Margolis, Alessandro Sette, Matthew H. Collins, John Schmitz, and Ralph S. Baric.
This research was supported by the National Science Foundation (1250104, 1351692) and the National Institutes of Health (1U18EB029353-01, R21EY028397A).
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Illustration of the human antibody latching onto the receptor binding domain (RBD)
of the spike protein of SARS-CoV-2. CREDIT UNC School of Medicine.