Biomedical engineers from Duke University have devised a test that can quickly and easily determine if an individual’s neutralizing antibodies combat infection from various variations of COVID-19, such as Delta and the recently discovered Omicron variant.
The test could inform doctors how secure the patient is from emerging variants and those currently circulating in a community or, in the opposite direction what monoclonal antibodies are required to treat a COVID-19 patient. The test was described online December 3, in the journal Science Advances.
We currently really have no rapid way of assessing variations, nor do we know if they exist in a person, nor the ability of antibodies that we have to make a difference. One of the worries is that as we continue to immunize more people, a variant could be discovered that blocks the immune neutrization that is induced by vaccines. If this fear were to come true, how would we know fast enough to know if Omicron turned into the worst-case scenario?
Cameron Wolfe, Associate Professor of Medicine at Duke University School of Medicine
“While developing a point of care test for COVID-19 biomarkers as well as antibodies, we realized that there might be some benefits to being able to detect the capacity to neutralize certain variants of antibodies, so we built an experiment to test that idea,” Ashutosh Chilkoti is the Alan L.Kaganov Chair and Distinguished Professor in Biomedical Engineering at Duke. It took us only a few weeks to incorporate the Delta variant in the test. The test is easily extended to include the Omicron variant. We only need the spike protein from this variant that many research groups around the globe including our own at Duke are trying to produce.
The researchers have dubbed their test the COVID-19 Variant Spike-ACE2-Competitive Antibody Neutralization assay, or CoVariant-SCAN for short. The test’s technology hinges on a coating of polymer that acts as a kind of non-stick coating, which prevents anything other than the biomarkers you want from attaching to the slide test when it is wet. This shield is extremely effective and sensitive to low levels of targets. The method allows researchers to print different molecular traps onto different areas of the slide to catch multiple biomarkers at the same time.
In this application, researchers print fluorescent human ACE2 proteins – the cells that are the targets of the virus’s infamous spike protein–on a slide. They also print spike proteins that are unique to every COVID-19 variant in various locations. When the test is run the ACE2 proteins disengage from the slide and are caught by the spike proteins that remain attached to the slide. This causes the slide to glow.
However, in the presence of neutralizing antibodies, the spike proteins cannot hold onto the ACE2 proteins, which makes the slide appear less bright and indicating the effectiveness of the antibodies. Printing different versions of the COVID-19 spike protein on different areas of the slide, researchers can determine how efficient the antibodies are in preventing each variant from binding to their human cellular target simultaneously.
The paper provides a range of testing methods that the researchers used to test the technology. Monoclonal antibodies were either derived from real patients or Regeneron’s prophylactic treatment. They also evaluated plasma from healthy people who had been vaccinated and those who had been infected.
Jake Heggestad a PhD student in the Chilkoti lab said that “all of our tests largely correspond to what we’ve read in the literature.” “And in this instance, not finding anything new is a positive sign because it means that our test is working as well as the techniques currently being used.”
While they produce similar results, the main difference between CoVariant-SCAN and the current methods is the speed and ease at which it can produce results. Typical current approaches require the isolation of live virus and culturing cells, which could take up to up to 24 hours and requires a wide variety of safety precautions and specially trained technicians. The CoVariant SCAN is, unlike other approaches does not require live virus and can be used in most situations in less than an hour;potentially only 15 minutes–to produce accurate results.
Heggestad and the Chilkoti laboratory, and others are working together to streamline the process into an instrument that can be mass-produced and report results with only the drop of plasma, blood, or other liquid samples that contain antibodies. This method has been shown to be effective in the same test, which can differentiate COVID-19 from other coronaviruses.
Wolfe stated that he would love to be able to view the new variants in real time and be able to recognize those with functional immunity. “Additionally, this hints that there may be a method whereby you can quickly identify the type of monoclonal antibody that would be the best choice for patients suffering from an emergent variant. We currently have no real-time method of determining that, so we rely on epidemiological data that can monitor weeks in the past.”
“The reverse is also true,” Wolfe continued. “To be able to pre-screen an individual’s antibodies and determine whether they were sufficiently protected from a specific variant they may encounter on their travels, or that is emerging in their region. At the moment, we don’t have the ability to do that. However, a test such as the CoVariant SCAN could allow these scenarios to be realized.
Heggestad J.T. et. and. (2021). Rapid Test to Determine the Escape from SARS-Cov-2 Variants of Concern. Science Advances. doi.org/10.1126/sciadv.abl7682.
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