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Wash U Researchers Genetically Engineer Coronavirus Lookalike

Matt Miller
Washington University
Paul Rothlauf, a graduate student and visiting scientist at Washington University, helped develop the genetically engineered virus using a common livestock virus that doesn't cause serious illness in humans. The new hybrid virus behaves like the coronavirus but is much safer to work with in the lab — and could eventually form the basis of a coronavirus vaccine.

Scientists need a lot of safety equipment to study the coronavirus in a research lab: biohazard suits, respirators, custom airflow systems.

Not every lab meets the safety standards to work with potentially lethal viruses — and getting certified can take years.

“There isn't really enough capacity for the current demand to work with SARS-CoV-2, so it’s created a bottleneck,” said Sean Whelan, a microbiology professor and virologist at Washington University.

To allow more labs to conduct coronavirus research, Whelan and a team of Washington University researchers devised a workaround: a genetically engineered virus.

Created using a common livestock virus, the hybrid virus is covered in spiky proteins identical to those of the coronavirus, allowing it to invade human cells in a similar way. Though the new virus behaves like the coronavirus, it’s much safer to work with in the lab — and could eventually form the basis of a coronavirus vaccine.

Like other viruses, the coronavirus has a crown of protein spikes adorning its surface that it uses to attach to and infect cells. Our immune system creates antibodies that bind to these proteins and slow the spread of the virus.

To create a faux coronavirus that would fool our immune systems, the Wash U team used vesicular stomatitis, a widespread virus that usually infects horses and cattle and can cause mild flu-like symptoms in humans.

Then they swapped in coronavirus genes that encode for its spike proteins, essentially slipping a coronavirus protein coat over the livestock virus to disguise it.

“It looks like the coronavirus on the outside, but on the inside, it's vesicular stomatitis virus,” Whelan explained. “Therefore, it's seen by the immune system as SARS-CoV-2.”

Centers for Disease Control and Prevention
The coronavirus known as SARS-CoV-2 causes COVID-19 in humans. Coronaviruses are named for the crown of spike proteins on their surfaces, shown here, which allow the viruses to infect cells.

The hybrid virus was also able to infect cells in a way similar to the coronavirus, said Paul Rothlauf, a graduate student who worked on the study.

“Because our virus displays the coronavirus protein instead of its own, it now enters cells identically to how the actual coronavirus would,” Rothlauf said. “Basically, you can use this as a tool to screen for drugs or small molecules that inhibit viral entry into the cell.”

A possible coronavirus vaccine

The applications of the engineered livestock virus may eventually go beyond the laboratory. The team is now eyeing it as a possible coronavirus vaccine candidate and has completed an initial round of testing in mice.

Based on preliminary results, when mice are vaccinated with the hybrid virus, their immune systems are better able to fight off the coronavirus later.

“We've seen robust antibody production in mice that are vaccinated with this vaccine,” Rothlauf said. “When you challenge vaccinated animals with the coronavirus, you can’t detect any replicating infectious SARS-CoV-2 virus from the lungs of these animals after a few days of challenge.”

“It looks like the coronavirus on the outside, but on the inside, it's vesicular stomatitis virus."
Sean Whelan, microbiology professor at Washington University

Using vesicular stomatitis as a backbone for the vaccine has several advantages. The virus replicates rapidly in the lab and can grow in the specialized primate kidney cells used for vaccine production, Whelan said.

“It's all very well to develop a vaccine candidate that works wonderfully in the laboratory setting or in preclinical testing,” he said. “But if you can't scale the production up to be able to produce hundreds of millions of doses, then all that work was for nothing.”

Several other companies are now developing their own coronavirus vaccines using vesicular stomatitis, including Merck, which has received more than $38 million in funding from the federal government. Merck used a similar approach to develop an Ebola vaccine, the first to receive FDA approval.

Despite the race to develop a coronavirus vaccine, the Wash U team has opted to share the engineered virus with researchers in other countries, including Argentina, Brazil, Mexico and Canada.

“The majority of the requests that we've had are so that people can screen serum from patients and look for levels of neutralizing antibodies to test whether people are potentially immune,” Whelan said. “It's wonderful to be able to generate something that is broadly useful.”

Follow Shahla on Twitter: @shahlafarzan

Shahla Farzan was a reporter at St. Louis Public Radio. Before becoming a journalist, Shahla spent six years studying native bees, eventually earning her PhD in ecology from the University of California-Davis. Her work for St. Louis Public Radio on drug overdoses in Missouri prisons won a 2020 Regional Edward R. Murrow Award. 

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