04/30/2003

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OARDC Scientist Contributes to SARS Research, Quest for Vaccine

Writer:

Mauricio Espinoza
espinoza.15@osu.edu
(330)202-3550

Source:

David Benfield
benfield.2@osu.edu
(330)263-3702

Linda Saif
saif.2@osu.edu
(330)263-3742

WOOSTER, Ohio -- Ohio State University researcher Linda Saif has joined a group of scientists led by the U.S. Centers for Disease Control and Prevention (CDC) in an effort to characterize the coronavirus responsible for severe acute respiratory syndrome (SARS) and pave the way to the development of an effective vaccine.

A virologist with the university's Ohio Agricultural Research and Development Center (OARDC) in Wooster, Saif is a world expert on pathogens that cause intestinal and respiratory diseases in food-producing animals, including rotaviruses, caliciviruses and coronaviruses.

"They (CDC scientists) are very interested in knowing more about the pathogenesis studies for animal coronaviruses that we have done," said Saif, a professor and researcher with OARDC's Food Animal Health Research Program (FAHRP). "They are also quite interested in our experience with animal coronavirus vaccines, what approaches have been used to develop them and how effective they are."

With 30 years of experience as a coronavirologist, Saif was asked to join a select group of physicians and virus experts from CDC, the National Institutes of Health (NIH) and other institutions. The team, which meets two times a week by teleconference to discuss and make recommendations on the acute respiratory syndrome, is at the forefront of SARS control in the United States.

"I have been exchanging a lot of e-mails with the whole CDC SARS group, trying to fill them in on research findings related to my expertise and the experience I have had working with the bovine and porcine coronaviruses," Saif said. "We have also sent them a lot of animal coronavirus reagents for coronavirus detection and characterization studies."

The reagents sent to CDC include antisera and monoclonal antibodies to the porcine transmissible gastroenteritis virus (TGEV) and the bovine coronavirus (BCV). Saif's lab is recognized worldwide for the development of diagnostic tests and vaccines for these viruses, which cause high mortality and morbidity in pigs and cattle.

"CDC is using those reagents to see if any of them would cross-react and recognize the SARS coronavirus," Saif explained. "That might tell them if the SARS coronavirus is similar to any of the known animal coronaviruses or if it shares some common antigenic site that would be recognized by antibodies.

"It appears that the SARS coronavirus does react with some of the antibodies to TGEV, the feline infectious peritonitis virus and the human coronavirus 229-E," Saif added. "However, the basis for this cross-reactivity is not yet understood, since the genetic sequence of the SARS coronavirus shows that this is a novel coronavirus, genetically unrelated to TGEV, BCV or other known animal coronaviruses. CDC will analyze our reagents to see if there's any commonality between the human and animal strains of the coronavirus that could be exploited in terms of diagnostic tests or vaccine development."

Although TGEV and BCV have been long associated with gastrointestinal diseases in animals, it has been discovered in the past few years that these pathogens can also cause respiratory diseases. This aspect of both coronaviruses is also of interest to CDC.

"We have done many studies to see if this respiratory variant of TGEV (porcine respiratory coronavirus) can be developed as a possible vaccine to prevent TGEV," Saif said. "In the process, we have learned a lot about the types of immune responses that the respiratory coronavirus can induce in pigs. And we are thinking that pigs might have potential to be utilized in the future as an animal model for SARS coronavirus in humans."

Cattle could also become an important animal model in the search for a SARS vaccine. Seven years ago, Saif, her graduate students and co-workers were among the first to show that the bovine coronavirus is associated with shipping fever disease, which causes pneumonia in feedlot cattle.

"The shipping fever disease complex resembles some of the epidemiologic features of the SARS coronavirus," Saif pointed out. "Just like cattle, people who caught SARS were exposed to the virus by coming in close contact with other infected individuals, and many had traveled some distance, which is a stress factor. After cattle are transported to the feedlot, they usually start shedding the virus and come down with the disease within a week of arrival, so the incubation period for both viruses is very similar."

Saif added that the pneumonia associated with BCV is similar to the pneumonia experienced by some SARS patients. Moreover, some people affected by SARS have developed gastroenteritis in addition to respiratory disease, which has been the case with some cattle struck by shipping fever disease.

Finding an easy-to-use, economical animal model for SARS is key to the success of future research on the virus, said David Benfield, OARDC associate director and longtime coronavirus and arterivirus researcher. FAHRP's gnotobiotic animal facility -- in which germfree pigs and calves are used to analyze viruses, study how they cause disease and test vaccines -- has great potential for similar studies with the SARS coronavirus. The facility is one of only a few worldwide.

However, OARDC's future contributions to SARS research may not be as extensive as Saif and Benfield would like them to be. The center lacks a biosafety containment level 3, or BL-3, facility, which is required to handle live infectious pathogens such as the SARS coronavirus. For now, the only studies Saif can conduct are with inactivated or non-infectious fragments of the virus or its nucleic acid.

"We are hoping to receive funding for a BL-3 facility, but that's not available yet," Saif said. "This obviously is a handicap and frustrating because we have all this knowledge and background working with coronaviruses, but we don't have the facilities that would allow us to pursue this work."

According to Benfield, OARDC is looking into establishing research collaborations with other Midwestern universities that have BL-3 facilities.

An Ohio State Distinguished University Professor, Saif has received numerous awards during her career, including an honorary doctorate from Belgium's Ghent University. This week, she was elected member of the National Academy of Sciences, one of the highest honors that can be accorded a U.S. scientist or engineer.

OARDC is the research arm of Ohio State's College of Food, Agricultural, and Environmental Sciences.

Editor's Note: To arrange interviews with Linda Saif, please contact Mauricio Espinoza at (330) 202-3550 or espinoza.15@osu.edu. Photographs and an audio interview are available.