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UNC, Vanderbilt discover a new live vaccine approach for SARS and novel coronaviruses
Date:11/12/2012

anderbilt University School of Medicine, and Ralph Baric, Ph.D., professor of Microbiology, Immunology and Epidemiology at the University of North Carolina at Chapel Hill's Gillings School of Global Public Health. The researchers' aim is to better understand how coronaviruses, which also cause the common cold, evolve and spread between species.

Denison's lab developed the attenuated SARS virus by disabling a unique exoribonuclease (or ExoN) protein, referred to as a proofreading protein. Previous Vanderbilt studies had shown that disabling ExoN knocks out the virus's ability to correct mistakes, increases mutations twentyfold, and stops its ability to cause disease, at least in the lab setting. Graham, formerly a graduate student in Denison's lab, was able to continue the work in animal models as a postdoctoral scientist in Baric's lab.

Coronaviruses are RNA viruses known to have the largest genomes in the RNA viral world. It is now understood that the ExoN proofreading protein allows coronaviruses to maintain their expanded genomes, with many proteins evolved to help them survive and spread. But deactivation of ExoN creates a particularly enticing potential approach to vaccine design.

"Live vaccines in general confer broader and longer-lasting immunity, but the risk of live vaccines is they could potentially revert back to virulence as happened with the live polio vaccine in immunocompromised people," Baric said. "Our evidence is exciting because a more permanently attenuated virus might be safer. We believe that related approaches can be applied to other important human and animal viruses, resulting in safer vaccines."

To test the likelihood of reversion to virulence, researchers allow a virus to grow in a host that lacks immunity. In the current study, even in very young, very old and immunocompromised animals, the virus did not kill and could persist for a long time without showing signs of a return to virulence.

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Contact: Carole Bartoo
carole.bartoo@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert

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