Rapid test identifies efficacy of antibodies against COVID-19 variants

Biomedical engineers at Duke University have designed a test to quickly and easily assess how well a person’s neutralizing antibodies fight infection with several COVID-19 variants such as Delta and the newly discovered Omicron variant.

This test could potentially tell doctors how protected a patient is against new variants and those currently circulating in a community or, conversely, which monoclonal antibodies to treat a COVID-19 patient. The test is described online Dec. 3 in the journal Science Advances.

“We currently have no rapid way to assess the variants, neither their presence in an individual, nor the ability of the antibodies we have to tell the difference,” said Cameron Wolfe, associate professor of medicine at Duke University School of Medicine. “It is one of the lingering fears that as we successfully vaccinate more and more people, a variant may emerge that more drastically escapes the vaccine-induced neutralization of antibodies. And if that fear came true – if Omicron turned out to be the worst-case scenario – how would we know soon enough? “

“While developing a point-of-care test for COVID-19 antibodies and biomarkers, we realized that there might be an advantage in being able to detect the ability of antibodies to neutralize specific variants, so we built a test around this idea, “said Ashutosh Tchilkoti, Professor Emeritus Alan L. Kaganov and Chair of Biomedical Engineering at Duke. “It only took us a week or two to incorporate the Delta variant into our test, and it could easily be extended to include the Omicron variant as well. All we need is this variant’s spike protein, which many groups around the world, including our group at Duke, are feverishly working to produce.

The researchers dubbed their test the COVID-19 Variant Spike-ACE2-Competitive Antibody Neutralization test, or CoVariant-SCAN for short. The test technology relies on a polymer brush coating that acts as a kind of non-stick coating to prevent anything but the desired biomarkers from attaching to the test slide when wet. The high efficiency of this non-stick shield makes the test incredibly sensitive even at low levels of its targets. The approach allows researchers to print different molecular traps on different areas of the slide to capture multiple biomarkers at once.

The new test for the effectiveness of antibodies against several variants of COVID-19 works by releasing fluorescently labeled ACE2 proteins – the cellular targets of the COVID-19 spike protein – with antibodies. While the antibodies are able to neutralize the COVID-19 spike protein variants imprinted on the slide, they cannot bind to the ACE2 proteins, resulting in the removal of fluorescent markers and obscuration of the slide.

In this application, researchers print human ACE2 fluorescent proteins, the cellular targets of the virus’s famous spike protein, onto a slide. They also print spike proteins specific to each variant of COVID-19 in different specific places. When the test is run, the ACE2 proteins break away from the slide and are captured by the spike proteins still attached to the slide, causing the slide to glow.

But in the presence of neutralizing antibodies, the spike proteins are no longer able to attach to the ACE2 proteins, which makes the slide less shiny, indicating the effectiveness of the antibodies. By imprinting different variants of the COVID-19 spike protein on different parts of the slide, researchers can see how effective the antibodies are at preventing each variant from simultaneously attaching to their human cellular target.

In the article, the researchers tested the technology in different ways. They tried monoclonal antibodies derived from real patients or the commercial Regeneron prophylactic treatment. They also tested plasma taken from healthy vaccinated people and those currently infected with the virus.

“In all of our tests, the results largely mimicked what we’ve seen in the literature,” said Jake Heggestad, a doctoral student working in Chilkoti’s lab. “And in this case, not finding anything new is a good sign, because it means that our test is working as well as the methods currently in use.”

Although they produce similar results, the critical difference between CoVariant-SCAN and current methods is the speed and ease with which it can produce results. Typical current approaches require the isolation of live viruses and the cultivation of cells, which can take 24 hours or more and require a wide variety of safety precautions and specially trained technicians. The CoVariant-SCAN, on the other hand, does not require a live virus, is easy to use in most settings, and takes less than an hour, or even just 15 minutes, to produce accurate results.

Going forward, Heggestad and the Chilkoti lab are working to streamline the technique into a microfluidic chip that could be mass-produced and report results with just a few drops of blood, plasma, or other liquid samples containing antibodies. . This approach has already been proven to work on a similar test that can distinguish COVID-19 from other coronaviruses.

“We would like to have real-time visibility of emerging variants and understand who still has functional immunity,” Wolfe said. Additionally, it suggests that there may be a technique to quickly assess which synthetic monoclonal antibody would be best to administer to a patient with a particular emerging variant. Currently, we really have no way of knowing by. real time, so we rely on epidemiological data that can follow weeks of delay. ”

“The reverse is also true,” continued Wolfe. “To be able to pre-screen an individual’s antibodies and predict whether they were sufficiently protected against a particular variant that they may be about to encounter while traveling, or that emerges in their region.” We have no way of doing it right now. But a test like CoVariant-SCAN could make all of these scenarios possible. “

This work was supported by the National Institutes of Health (K08HL130557, R01 AI159992, P30-CA014236, UC6AI058607), the National Science Foundation (CBET2029361), and the Department of Defense / Defense Advanced Research Projects Agency (HR0011-17-2- 0069).

QUOTE: “Rapid Test to Evaluate Escape from Variants of Concern of SARS-Cov-2”, Jacob T. Heggestad, Rhett J. Britton, David S. Kinnamon, Simone A. Wall, Daniel Y. Joh, Angus M. Hucknall , Lyra B. Olson, Jack G. Anderson, Anna Mazur, Cameron R. Wolfe, Thomas H. Oguin III, Bruce A. Sullenger, Thomas W. Burke, Bryan D. Kraft, Gregory D. Sempowski, Christopher W. Woods, Ashutosh Tchilkoti. Science Advances, December 3, 2021. DOI: 10.1126 / sciadv.abl7682

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Sara H. Byrd