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

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 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.


'/>"/>

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

Related medicine news :

1. Vanderbilt study finds obesity linked to kidney injury after heart surgery
2. Vanderbilt researchers find proteins may point way to new prostate cancer drug targets
3. Vanderbilt-led study reveals racial disparities in prostate cancer care
4. Vanderbilt study looks at benefits of progestogens to prevent early childbirth
5. Scientist awarded $1 million grant to develop tools for hepatitis C treatment discovery
6. Washingtons Life Sciences Discovery Fund awards commercialization grants
7. Discovery could help to develop drugs for organ transplant and cancer patients
8. Feelings of immaturity accompany alcohol misuse into adulthood; discovery could improve treatments
9. IBN discovers human neural stem cells with tumor targeting ability
10. H1N1 discovery paves way for universal flu vaccine: UBC research
11. Researchers discover how to overcome poor response to radiotherapy caused by low haemoglobin levels
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... 2016 , ... A revolution is underway. Brooklyn-based company, ... for the millions of people who require these medical transport services annually. ... the use of technology. Now, SmartEMS has put forth an industry-changing app that ...
(Date:6/26/2016)... ... June 26, 2016 , ... On June 10-11, 2016, A Forever ... Cereal Festival and World’s Longest Breakfast Table in Battle Creek, MI, where the rehabilitation ... as home to some of the world’s leading providers of cereal and other breakfast ...
(Date:6/26/2016)... ... June 26, 2016 , ... Brent Kasmer, a legally blind and certified personal trainer is ... a fitness app. The fitness app plans to fix the two major problems leading the ... one size fits all type program , They don’t eliminate all the reasons ...
(Date:6/25/2016)... Austin, TX (PRWEB) , ... June 25, 2016 , ... ... Fellow of the American College of Mohs Surgery and to Dr. Russell Peckham for ... popular and highly effective treatment for skin cancer. The selective fellowship in Mohs Micrographic ...
(Date:6/25/2016)... ... , ... First Choice Emergency Room , the largest network of independent ... Director of its new Mesquite-Samuell Farm facility. , “We are pleased to announce ... Dr. James M. Muzzarelli, Executive Medical Director of First Choice Emergency Room. , ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... -- The Academy of Managed Care Pharmacy (AMCP) today ... allow biopharmaceutical companies to more easily share health care ... coverage decisions, a move that addresses the growing need ... The recommendations address restrictions in the sharing of product ... a prohibition that hinders decision makers from accessing HCEI ...
(Date:6/24/2016)... Mass. , June 24, 2016   Pulmatrix, ... pharmaceutical company developing innovative inhaled drugs, announced today that ... Russell Investments reconstituted its comprehensive set of ... "This is an important milestone for Pulmatrix," ... will increase shareholder awareness of our progress in developing ...
(Date:6/23/2016)... HILLS, Calif. , June 23, 2016 Any ... the many challenges of the current process. Many of them ... because of the technical difficulties and high laboratory costs involved. ... have to offer it at such a high cost that ... afford it. Dr. Parsa Zadeh , founder ...
Breaking Medicine Technology: