Researchers at the University of Texas Medical Branch have identified proteins in the novel coronavirus that inhibit the body’s immune response, enabling development of COVID-19.
The findings will enable scientists to create engineered viruses, minus those proteins, that could lead to an effective vaccine against the disease that has so far contributed to 210,000 U.S. deaths and more than 1 million people worldwide, said Pei-Yong Shi, professor of biochemistry and molecular biology at the medical branch.
“The most practical application for this research is for a vaccine,” Shi said.
The results of the study, largely conducted in the National Laboratory at Galveston’s secure facility, were published this week in the journal Cell Reports.
A live-attenuated vaccine is one that uses a weakened form of the germ that causes a disease.
Some examples of successful ones are vaccines for yellow fever and measles, Shi said.
“The SARS-2 coronavirus and other viruses, in order to survive, develop strategies to inhibit our immune response,” Shi said. “For this specific study, what we systematically investigated were the proteins in the SARS-2 virus that have the ability to inhibit or suppress or fight back our bodies’ immune response.”
The research team first identified the proteins, then looked at the different ways those proteins block interferon, the body’s first line of defense against viral infection, from working.
Engineered viruses, minus those key proteins, could become a vaccine agent, basically a weaker version of SARS-coV-2 that, when injected into the body, would enable the body’s immune response to be triggered more quickly and effectively.
Scientists at the medical branch were the first to develop a reverse genetic system to engineer viruses, a process of mutating or changing specific characteristics of viruses in the lab, Shi said. The research team’s next task will be to manufacture the protein-stripped, engineered SARS-CoV-2 virus.
“Now that we know which proteins inhibit the body’s interferon, we are working on making or engineering viruses in which they have been taken out,” he said. “We’ll have them, then test whether it is true, that in an animal model, these engineered viruses could serve as a vaccine candidate.”
The vaccines in phase 3 clinical trials around the country don’t work in the same way that this live-attenuated vaccine would work, Shi said.
“What we’re doing is a completely new concept, to provide a complementary platform, a new platform, a second-generation vaccine,” he said.
Key findings in the study were that proteins from different coronaviruses have different levels of potency in inhibiting interferon response. While it was known that SARS-CoV-2, the virus that causes COVID-19, induced a delayed interferon response, the exact mechanism that caused that response was poorly understood before this study, according to the article in Cell Reports..
“My hope is that people will understand the virus better as well as ways to fight it,” Shi said. “The human lifespan has expanded so much over the past 50 years, and the main contributing factors to that were hygiene — cleaner food and water — and developing and using vaccines against diseases.”