Featured Research

from universities, journals, and other organizations

New live vaccine approach for SARS and novel coronaviruses discovered

Date:
November 12, 2012
Source:
Vanderbilt University
Summary:
Researchers have found that accelerating the rate of mutations in the coronavirus responsible for deadly severe acute respiratory syndrome cripples the virus's ability to cause disease in animals.

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.

Related Articles


A collaborative study, published Nov. 11 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 final tally: 8,422 cases of SARS, resulting in 916 deaths.

"We originally thought that the virus might find a way to fix the mutations we engineered or work around them as viruses often do. That didn't happen, and in this case, the attenuated viruses replicated well enough and long enough to generate a protective immune response, even in immunocompromised animals, so it works wonderfully as a vaccine in an animal model," said Rachel Graham, Ph.D., a research associate at UNC, who led the research.

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. 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.

"In contrast to science fiction, where mutations are evil and endanger the world, our studies demonstrate that viruses have evolved to tightly control their mutation rates, and changing that rate is detrimental to virus survival and disease in nature,"

Denison said. "Since all coronaviruses have the ExoN protein, this method for attenuation could be broadly applicable in coronaviruses."

"If we can't have a vaccine ready to administer that works for all coronaviruses, then we at least have a strategy for fast production of a functional vaccine for any new epidemic coronavirus that might arise. That's a key take-away point of our paper and what makes it so important in the face of current events," Graham said.


Story Source:

The above story is based on materials provided by Vanderbilt University. The original article was written by Carole Bartoo. Note: Materials may be edited for content and length.


Journal Reference:

  1. Rachel L Graham, Michelle M Becker, Lance D Eckerle, Meagan Bolles, Mark R Denison, Ralph S Baric. A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease. Nature Medicine, 2012; DOI: 10.1038/nm.2972

Cite This Page:

Vanderbilt University. "New live vaccine approach for SARS and novel coronaviruses discovered." ScienceDaily. ScienceDaily, 12 November 2012. <www.sciencedaily.com/releases/2012/11/121112113131.htm>.
Vanderbilt University. (2012, November 12). New live vaccine approach for SARS and novel coronaviruses discovered. ScienceDaily. Retrieved October 30, 2014 from www.sciencedaily.com/releases/2012/11/121112113131.htm
Vanderbilt University. "New live vaccine approach for SARS and novel coronaviruses discovered." ScienceDaily. www.sciencedaily.com/releases/2012/11/121112113131.htm (accessed October 30, 2014).

Share This



More Plants & Animals News

Thursday, October 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How A Chorus Led Scientists To A New Frog Species

How A Chorus Led Scientists To A New Frog Species

Newsy (Oct. 30, 2014) A frog noticed by a conservationist on New York's Staten Island has been confirmed as a new species after extensive study and genetic testing. Video provided by Newsy
Powered by NewsLook.com
Surfer Accidentally Stands on Shark, Gets Bitten

Surfer Accidentally Stands on Shark, Gets Bitten

AP (Oct. 30, 2014) A 20-year-old competition surfer said on Thursday he accidentally stepped on a shark's head before it bit him off the Australian east coast. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Raw: Dallas Zoo Welcomes Baby Male Giraffe

Raw: Dallas Zoo Welcomes Baby Male Giraffe

AP (Oct. 30, 2014) The Dallas Zoo has a new giraffe with the birth of a healthy male calf. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Endangered Carpathian Ponies Are Making a Comeback in Poland

Endangered Carpathian Ponies Are Making a Comeback in Poland

AFP (Oct. 29, 2014) At the foot of the rugged Carpathian mountains near the Polish-Ukrainian border, ranchers and scientists are trying to protect the Carpathian pony, known as the Hucul in Polish. Duration: 02:17 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins