The test can simultaneously measure the patient’s immunity to multiple COVID-19 variants such as Omicron and Delta, and inform which synthetic monoclonal antibody to use for treatment

Image: A new test can quickly test the ability of antibodies to neutralize spike proteins from different COVID-19 variants at the same time. The D4 test shown here is a Teflon-like technology that makes the test possible. see more 

Durham, North Carolina — Biomedical engineers at Duke University designed a test that can quickly and easily assess a person’s neutralizing antibodies against COVID-19 multiple variants (such as Delta and the newly discovered Omicron variant ) The ability to infect.

The test may tell doctors how to protect patients from new variants and variants currently circulating in the community, or, conversely, it may tell doctors which monoclonal antibodies can treat patients with COVID-19. The test was published online in the journal Science Advances on December 3.

Cameron Wolf, an associate professor of medicine at Duke University School of Medicine, said: "We really don't have a way to quickly assess mutations, whether it is their presence in individuals or the ability of antibodies we have to have an impact." "When we succeed. As more and more people are vaccinated, a lingering worry may arise to more completely avoid the neutralization of antibodies caused by the vaccine. If this fear comes true-if Omicron proves to be Worst case scenario-how can we know fast enough?"

"In developing point-of-care tests for COVID-19 antibodies and biomarkers, we realized that being able to detect antibodies' ability to neutralize specific variants might bring some benefits, so we built a test around this idea," Ashutosh Chilkoti, Alan L. Kaganov Distinguished Professor and Dean of the Department of Biomedical Engineering, Duke University. "It only took us a week or two to include the Delta variant in our tests, and it can be easily expanded to include the Omicron variant. All we need is the spike protein of this variant. Many teams around the world- Including our team at Duke-they are all producing like crazy."

The researchers call their test the COVID-19 Variant Spike-ACE2-Competitive Antibody Neutralization test, or CoVariant-SCAN for short. The technique of the test relies on a polymer brush coating, which acts as a non-stick coating that prevents anything other than the desired biomarker from adhering to the test slide when wet. The efficiency of this non-stick protective cover makes the test very sensitive to even low-level targets. This method allows researchers to print different molecular traps on different areas of the slide to capture multiple biomarkers at once.

In this application, the researchers printed the fluorescent human ACE2 protein, the cellular target of the virus's infamous spike protein, on a glass slide. They also printed spike proteins specific to each COVID-19 variant at different specific locations. When running the test, the ACE2 protein is separated from the slide and is captured by the spike protein still attached to the slide, making the slide glow.

But in the presence of neutralizing antibodies, the spike protein can no longer grasp the ACE2 protein, making the slide less luminous, indicating the effectiveness of the antibody. By printing different variants of the COVID-19 spike protein on different parts of the slide, researchers can see how effective the antibody is in preventing each variant from simultaneously locking onto its human cell target.

In the paper, the researchers tested the technology in many different ways. They tried monoclonal antibodies from real patients or commercial preventive treatments from Regeneron. They also tested plasma extracted from healthy vaccinated people and people currently infected with the virus.

"In all our tests, the results largely mimic what we see in the literature," said Jake Heggestad, a doctoral student working in Chilkoti's laboratory. "In this case, not discovering anything new is a good sign because it means that our tests are as effective as the methods currently used."

Although they produce similar results, the key difference between CoVariant-SCAN and the current method is the speed and ease with which it produces results. Current typical methods require isolation of live viruses and cultured cells, which may take 24 hours or more, and require various safety precautions and specially trained technicians. In contrast, CoVariant-SCAN does not require live viruses, is easy to use in most cases, and takes less than an hour (perhaps 15 minutes) to produce accurate results.

Looking to the future, Heggestad and Chilkoti laboratories are working to simplify this technology into a microfluidic chip that can be mass-produced and reported results with only a few drops of blood, plasma or other liquid samples containing antibodies. This method has been proven to be suitable for similar tests and can distinguish COVID-19 from other coronaviruses.

"We want to understand the emerging mutations in real time and understand who is still functionally immune," Wolff said. "In addition, this implies that there may be a technology through which you can quickly assess which synthetic monoclonal antibody is most suitable for patients with specific emergency mutations. Currently we really don’t have a real-time method to know this, so we Rely on epidemiological data that can be tracked several weeks later."

"The reverse is also true," Wolfe continued. “In order to be able to pre-screen a person’s antibodies and predict whether they are adequately protected against specific variants that they may encounter when traveling or appear in their area. We currently have no way to do this. But tests like CoVariant-SCAN can make all 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 (HR0011-009-16-17). support).

Citation: "A quick test to assess the escape of SARS-Cov-2 attention variants", 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 Elcotti. Progress in Science, December 3, 2021. DOI: 10.1126/sciadv.abl7682

A quick test to evaluate the escape situation of SARS-Cov-2 attention variants

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Ken Kingery Duke University ken.kingery@duke.edu Office: 919-660-8414

Ashutosh Chilkoti Pratt School of Engineering, Duke University ashutosh.chilkoti@duke.edu

Jake Heggestad Pratt School of Engineering, Duke University jacob.heggestad@duke.edu

Copyright © 2021 American Association for the Advancement of Science (AAAS)

Copyright © 2021 American Association for the Advancement of Science (AAAS)