Airborne and potentially deadly, the virus which causes COVID-19 can only be studied safely under high level biosafety conditions. Scientists handling the virus that is infectious must wear full-body biohazard matches with pressurized respirators, and operate inside labs with multiple containment degrees and technical ventilation systems. While necessary to protect laboratory employees, these security precautions slow down efforts to find vaccines and drugs for COVID-19 since many scientists lack access to the required biosafety facilities.

To help remedy this, researchers at Washington University School of Medicine in St. Louis have developed a hybrid virus that may enable more scientists to go into the fight against the pandemic. The researchers modified a moderate virus by swapping one of its own genes for one from SARS-CoV-2, the virus that leads to COVID-19. The resulting hybrid cells and can be recognized by antibodies just like SARS-CoV-2, but can be handled under normal laboratory security requirements.

The study is available online in Mobile Host &amp; Microbe.

"I've never had this many requests for a scientific material in this short time period," stated co-senior writer Sean Whelan, PhD, the Marvin A. Brennecke Distinguished Professor and head of the Department of Molecular Microbiology. "We have distributed the virus to investigators in Argentina, Brazil, Mexico, Canada and, of course, throughout the U.S.. We have requests pending from the U.K. and Germany. Even before we published, people heard that we had been working on this and started asking the material."

To create a model of SARS-CoV-2 that will be safer to handle, Whelan and colleagues -- including co-senior writer Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine, and co-first writers Brett Case, PhD, a postdoctoral researcher in Diamond's lab, and Paul W. Rothlauf, a graduate student in Whelan's laboratory -- began with vesicular stomatitis virus (VSV). This virus is a workhorse of virology labs because it is fairly innocuous and easy to manipulate . Primarily a virus of cattle, horses and horses, VSV occasionally infects people, causing a mild flu-like disease that lasts three to four days.

The researchers eliminated VSV's surface-protein gene and replaced it with the one from SARS-CoV-2, called spike. The switch produced a new virus that targets cells such as SARS-CoV-2 but lacks the other genes needed to cause acute illness. They called the hybrid VSV-SARS-CoV-2.

Using serum from COVID-19 survivors and purified antibodies, the researchers revealed that the hybrid was recognized by antibodies much like a real SARS-CoV-2 virus which came out of 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 this; electrons or sera that failed to block the hybrid also failed to dissuade the real SARS-CoV-2. In addition, a decoy molecule was effective at misdirecting both viruses and preventing them from infecting cells.

<span style="color: #ff6600;"><a style="color: #ff6600;" href="https://www.sciencedirect.com/science/article/pii/S1931312820303620?via%3Dihub">"People certainly grow antibodies against other SARS-CoV-2 proteins, but it's the radicals against spike that appear to be most important for protection," Whelan said. "</a></span>So as long as a virus has the spike protein, then it appears to the individual immune system like SARS-CoV-2, for all intents and purposes."

The hybrid virus could help scientists evaluate a range of antibody-based preventives and treatments for COVID-19. The virus may be used to evaluate whether an experimental vaccine elicits neutralizing antibodies, to measure whether or not a COVID-19 survivor carries enough neutralizing antibodies to contribute plasma to COVID-19 sufferers to identify antibodies with the potential to be developed into antifungal drugs.

<span style="color: #ff6600;"><a style="color: #ff6600;" href="https://www.sciencedirect.com/science/article/pii/S1931312820303620?via%3Dihub">"Among the issues in assessing neutralizing antibodies is that a good deal of these tests need a BSL-3 facility, and many 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.</a></span> "With this virus, you can take serum, plasma or antibodies and do high-throughput analyses at BSL-2 amounts, which each lab has, with no risk of becoming infected. And we all know that it correlates almost perfectly with all the data we get from bona fide infectious SARS-CoV-2."

Since the hybrid virus looks like SARS-CoV-2 to the immune system but doesn't cause severe illness, it is a possible vaccine candidate, Diamond added. He, Whelan and colleagues have been conducting animal studies to assess the possibility.

<strong>Story Source:</strong>

<span style="color: #ff6600;"><a style="color: #ff6600;" href="https://www.sciencedirect.com/science/article/pii/S1931312820303620?via%3Dihub">Materials</a></span> provided by Washington University School of Medicine. Original written by Tamara Bhandari. Note: Content may be edited for style and length.

<strong>Journal Reference:</strong>

James Brett Case, Paul W. Rothlauf, Rita E. Chen, Zhuoming Liu, Haiyan Zhao, Arthur S. Kim, Louis-Marie Bloyet, Qiru Zeng, Stephen Tahan, Lindsay Droit, Ma. Xenia G. Ilagan, Michael A. Tartell, Gaya Amarasinghe, Jeffrey P. Henderson, Shane Miersch, Mart Ustav, Sachdev Sidhu, Herbert W. Virgin, David Wang, Siyuan Ding, Davide Corti, Elitza S. Theel, Daved H. Fremont, Michael S. Diamond, Sean P.J. Whelan. Neutralizing antibody and soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2.. Cell Host &amp; Microbe, 2020; <span style="color: #ff6600;"><a style="color: #ff6600;" href="https://www.sciencedirect.com/science/article/pii/S1931312820303620?via%3Dihub">DOI: 10.1016/j.chom.2020.06.021</a></span>