Lab-Made COVID-19 Virus Helps Scientists Develop Drugs and Vaccines Under Ordinary Laboratory Safety Conditions

A lab-made virus that infects cells and interacts with antibodies just like the COVID-19 virus, but lacks the ability to cause severe disease has made it possible for scientists who do not have access to high-level biosafety facilities to join the effort to find drugs or vaccines for COVID-19.

Researchers at the Washington University School of Medicine (St. Louis, MO, USA) have developed a hybrid virus dubbed VSV-SARS-CoV-2 that will enable more scientists to enter the fight against the pandemic. The researchers genetically modified a mild virus by swapping one of its genes for one from SARS-CoV-2, the virus that causes COVID-19. The resulting hybrid virus infects cells and is recognized by antibodies just like SARS-CoV-2, but can be handled under ordinary laboratory safety conditions.

To create a model of SARS-CoV-2 that would be safer to handle, the researchers started with the vesicular stomatitis virus (VSV) as it is fairly innocuous and easy to manipulate genetically. Primarily a virus of cattle, horses and pigs, VSV occasionally infects people, causing a mild flu-like illness that lasts three to five days. Viruses have proteins on their surfaces that they use to latch onto and infect cells. The researchers removed VSV’s surface-protein gene and replaced it with the one from SARS-CoV-2, known as spike. The switch created a new virus that targets cells like SARS-CoV-2 but lacks the other genes needed to cause severe disease.

Using serum from COVID-19 survivors and purified antibodies, the researchers showed that the hybrid virus was recognized by antibodies very much like a real SARS-CoV-2 virus that came from a COVID-19 patient. Antibodies or sera that prevented the hybrid virus from infecting cells also blocked the real SARS-CoV-2 virus from doing so; antibodies or sera that failed to stop the hybrid virus also failed to deter the real SARS-CoV-2. In addition, a decoy molecule was equally effective at misdirecting both viruses and preventing them from infecting cells. The hybrid virus could help scientists evaluate a range of antibody-based preventives and treatments for COVID-19. The virus could be used to assess whether an experimental vaccine elicits neutralizing antibodies, to measure whether a COVID-19 survivor carries enough neutralizing antibodies to donate plasma to COVID-19 patients, or to identify antibodies with the potential to be developed into antiviral drugs.

“One of the problems in evaluating neutralizing antibodies is that a lot of these tests require a BSL-3 facility, and most clinical labs and companies don’t have BSL-3 facilities,” said co-senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine, and also a professor of molecular microbiology, and of pathology and immunology. “With this surrogate virus, you can take serum, plasma or antibodies and do high-throughput analyses at BSL-2 levels, which every lab has, without a risk of getting infected. And we know that it correlates almost perfectly with the data we get from bona fide infectious SARS-CoV-2.”

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Washington University School of Medicine