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AROUND THE MEDICAL CENTER :: WINTER 2014
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UNC, Vanderbilt discover a new live vaccine approach for SARS and novel coronaviruses


By Carole Bartoo
February 2013

Photo by iStockphoto.com

Photo by iStockphoto.com

Rapid mutation has long been considered a key to viral adaptation to environmental change. But in the case of the coronavirus responsible for deadly severe acute respiratory syndrome (SARS), collaborating researchers at the University of North Carolina and Vanderbilt University have found that accelerating the rate of mutations cripples the virus’s ability to cause disease in animals.


In addition, they say this finding may allow scientists to explore a new option for creating safer live vaccines.


A collaborative study, published Nov. 11, 2012, in Nature Medicine, demonstrates a SARS-coronavirus, altered to lack the ability to “proofread” (correct mistakes in replication), begins to mutate much more rapidly and becomes unable to cause disease in mouse models. In effect, the alteration creates a profoundly weakened or attenuated SARS virus.
This work may offer reassurance at a critical time. Public attention was recently heightened regarding a novel human coronavirus that sickened at least two with respiratory and kidney disease, killing one in the Middle East. The SARS outbreak in 2002 and 2003 caused 50 percent mortality in older adults. A rapid and effective international response ended the outbreak in just four months.


The researchers’ aim is to better understand how coronaviruses, which also cause the common cold, evolve and spread between species.
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.
The study is the culmination of more than a decade of collaboration between the laboratories of Mark Denison, M.D., Craig-Weaver Professor of Pediatrics and professor of Pathology, Microbiology & Immunology at Vanderbilt 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.

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