Posted on Jul 27, 2020, 6 p.m.
A hybrid virus has been created in a lab that infects cells and interacts with antibodies just as COVID-19 does, but this hybrid virus lacks the ability to cause severe disease making it safer for scientists that do not have access to high level biosafety facilities to study.
Without access to high level biosafety conditions the COVID-19 virus can’t be studied easily, scientists have to wear full body biohazard suits with pressurized respirators and work inside areas with multiple containment levels and specialized ventilation systems. These measures are necessary to protect lab workers and are slowing down efforts to find drugs for this virus as well as any other airborne and potentially deadly virus as many scientists lack access to the required biosafety facilities.
In a report published in Cell Host & Microbe researchers from the Washington University School Of Medicine St. Louis describe how they have been working to develop a hybrid virus to enable more scientists access to study this virus by genetically modifying it by switching one of the genes from SARS-CoV-2 with one from a milder virus; the resulting hybrid still infects cells and is recognized by antibodies as the original virus but it can be handled under ordinary lab safety conditions.
"I've never had this many requests for a scientific material in such a short period of time," said co-senior author Sean Whelan, PhD, the Marvin A. Brennecke Distinguished Professor and head of the Department of Molecular Microbiology. "We've distributed the virus to researchers in Argentina, Brazil, Mexico, Canada and, of course, all over the U.S. We have requests pending from the U.K. and Germany. Even before we published, people heard that we were working on this and started requesting the material."
To create the hybrid the team started with the vesicular stomatitis virus which is a workhorse of virology labs as it is fairly innocuous and easy to genetically manipulate. The VSV’s surface protein gene that latches onto other cells was removed and replaced with the one from SARS-CoV-2, and this switch created a new virus that targets cells like SARS-CoV-2 but lacks the genes needed to cause severe disease, and it has been dubbed hybrid virus VSV-SARS-CoV-2.
Purified antibodies and serum from survivors was used to test on the hybrid which showed that it was recognized by antibodies similar to the real virus coming from a COVID-19 patient. Sera/antibodies that prevented the hybrid from infecting cells also blocked the real virus from doing so, and those that failed to block the hybrid also failed to deter the real virus. Additionally, a decoy molecule was found to be able to misdirect both viruses equally and prevent them from infecting cells.
"Humans certainly develop antibodies against other SARS-CoV-2 proteins, but it's the antibodies against spike that seem to be most important for protection," Whelan said. "So as long as a virus has the spike protein, it looks to the human immune system like SARS-CoV-2, for all intents and purposes."
"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 Diamond, who is 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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