UTMB develops a system that could expedite a vaccine.
UTMB researchers develop system for expediting process
A team of researchers at the University of Texas Medical Branch in Galveston has developed a system that will allow scientists to expedite the process of developing and evaluating novel coronavirus vaccines, diagnose infected patients and screen potential antiviral drugs.
Led by Pei-Yong Shi, a professor of human genetics at the medical branch, the team built on a reverse genetic system that he created to manipulate the virus genome. Team members then used that system to create a clone of the coronavirus injected with a neon green fluorescent protein.
While adding color to a cloned virus may not sound like a groundbreaking development, scientists can use the green coronavirus clone to test the efficacy of a developing vaccine by placing the neon virus in a blood sample of a vaccinated individual. If the vaccine is ineffective, the infected cells will take on a greenish hue; if it is successful, the green virus will be diluted.
The development of the cloned green coronavirus could be crucial to determining whether a person already infected by the virus has antibodies that block the virus and prevent them from being reinfected. Testing for antibodies will help scientists determine what proportion of infected people were asymptomatic and also help pin
down a more accurate number of infections. It is widely assumed the number of people infected by the coronavirus is greater than what has been officially reported, particularly in the United States, which has tested less than 2 percent of its population.
“Just by looking at the color you will be able to tell in the specimen whether there is specific antibodies,” Shi told the Houston Chronicle. “This facilitates the detection, you can visually see it, it’s green and you can track where the viruses are.”
The antibody tests could also help government officials figure out how many people have gained immunity to the virus, which could guide decisions on when to lift social distancing restrictions and stay-at-home orders.
“When this (pandemic) calms down, when we start to return to social normality, then I think every organization would like to know, ‘Out of all my employees, who will be the safest to come back to work? Who is more vulnerable to infection?’ Those (decisions) can all be guided by the levels of antibodies in each individual,” Shi said. “It has a huge impact on when we exit the social distancing policy.”
Reverse genetic system
Shi, an expert on infectious diseases who has worked in both the private sector in the pharmaceutical industry as well as for the New York State Department of Health, has been at the forefront of researching the coronavirus’ complexities ever since the outbreak reached American soil.
In February, when the Centers for Disease Control and Prevention received its first virus sample from infected patients in Washington state and cultured it at its headquarters in Atlanta, the Galveston
National Laboratory at UTMB, a high-security biocontainment lab, was one of three labs in the country to receive the COVID-19 isolate.
Shi used that sample to develop a reverse genetic system to manipulate the virus genome, allowing scientists to essentially recreate the virus from scratch. The genetic system played a vital role in helping companies and hospitals all over the world develop badly needed diagnostic tests by stockpiling the genetic material needed to optimize tests for federal approval.
By establishing this reverse genetic system — and subsequently, the neon green cloned coronavirus — Shi hopes they can ascertain answers to the long list of “unknowns” about how the virus behaves: How contagious is it? How did it first infect humans? How quickly can our immune system develop antibodies?
“Once you establish that system, you can make and manipulate the pathogen on the petri dish,” Shi said. “So in the lab you can make mutant versions of the virus and you can really study it in many different aspects.”
Shi believes the genetic system and cloned coronavirus could be beneficial for diagnosing the virus in people by detecting antibodies much faster than normal serology tests, which typically take up to 10 days to turn around results.
Conventional methods of serology involve mixing the coronavirus with a blood sample. If the blood has antibodies, the antibodies will bind to the virus and prevent it from infecting blood cells. The catch is, because of the slow methodology, there is limited capacity for testing high volumes of blood specimens.
Shi said tests involving the green cloned coronavirus can be turned around much faster simply by virtue of it being tagged with a color. If a person’s blood doesn’t have antibodies, the cloned virus will infect the cell and turn it green. If an infected person’s blood has antibodies, those antibodies will bind to the cloned virus and the cell won’t turn green.
“You don’t have any capacity limitations,” Shi said. “It could be as short as three or four hours you get a result rather than a week.”
The same system can be used to screen and evaluate potential antiviral drugs to treat those infected with the coronavirus.
Pharmaceutical companies can use the cloned green virus to screen thousands of compounds to see which have the most activity inhibiting the virus. Again, if the drug compound does not inhibit the virus, the infected blood cells will turn green.
‘Huge advantage’
UTMB is already setting up studies to monitor infected patients for antibody levels, which he said would continue for at least two years.
The medical branch has also shared its reverse genetic system and the green cloned coronavirus with labs around the world. They are promoting the cloned virus to the CDC and New York State Department of Health officials for diagnostic testing, as well as pharmaceutical companies for drug screening.
If the system is validated by the Food and Drug Administration, Shi believes it could become the new standard for vaccine and drug evaluation.
“There is a huge advantage of having this reverse engineered system that we can really change the virus the way we want and use it to develop all kinds of things we want,” Shi said.
“That’s why I say, if it’s not the most important, it should be one of the most important tools people want to have to work on this virus.”