Joe Caspermeyer, Media Relations Manager & Science Editor
(480) 727-0369 | joseph.caspermeyer@asu.edu
June 24, 2008
Biodesign collaborative mettle leads to new SARS vaccine project
Biodesign Institute research assistant professor Zhong Huang recently received funding to lead a Severe Acute Respiratory Syndrome (SARS) vaccine project from the National Institute of Allergy and Infectious Disease, a branch of the National Institutes of Health.
During the two-year, $400,000 project, Huang and colleague Brenda Hogue, a Biodesign Institute and School of Life Sciences associate professor, will use tobacco plants to make large amounts of a segment from one of the SARS proteins that is important for infection. The segment is part of the surface of the SARS virus, called the spike protein, which is a major therapeutic target for researchers. By neutralizing the activity of spike, the Biodesign research duo hopes to prevent infection and thwart the progression of infection by the virus.
SARS became a major health threat in 2002, infecting more than 8,000 people worldwide. The mortality rate was 10 percent overall, and SARS is a major health threat to older individuals, mainly due to complications from pneumonia. It caused significant social and economic loses worldwide during the 2002-2003 outbreak.
When SARS emerged, no one could have predicted that a virus, usually the culprit of the common cold in humans, could become so harmful and spread so quickly worldwide from China to Canada. A newly emerged coronavirus was quickly identified as the cause of SARS. Fortunately, through heroic efforts of public health care organizations, the virus was contained.
Since then, global research teams have mobilized in an effort to understand the new virus and to develop a vaccine to prevent SARS. No vaccine is yet available. This makes the potential reemergence of SARS a great concern.
"With SARS-like related viruses being out there, there is certainly the possibility it will emerge again," said Hogue. "We were very fortunate SARS did not cause a widespread pandemic. There are many coronaviruses that circulate in a regular basis that infect a broad range of animals and humans, causing primarily respiratory and enteric diseases."
Coronaviruses invade cells in the human body with their spike proteins that poke out around the outer protective shell of the virus and fasten to cells like annoying cockleburs that stick to one’s socks from a walk in the woods.
The spike protein not only helps to cause infection, but looks under the microscope like a halo or crown that gives coronaviruses their namesake. After it attaches to the host cells, the virus then enters the cell and quickly hijacks the cell’s machinery to make more viral copies and spread the infection.
To increase their chances of success, the research team will hone in on the smallest portion of the spike protein that can attach to cells. This portion of the spike protein, called the receptor binding domain (RBD), interacts in a lock and key fashion with the receptors on the surface of the host cells. "This portion can elicit a strong immune response from the host. It has become a major target for a vaccine," said Huang.
"If one can really target and prevent interaction of the virus with the host receptor, then that’s a good first step toward protection," added Hogue.
The project is also a prime example of the Biodesign’s collaborative environment. About the same time SARS was running rampant, Huang and Hogue were newly recruited ASU and Biodesign researchers welcoming each other to the neighborhood.
Huang’s expertise is in plant virology. Hogue is a leading expert on coronaviruses. Now, their neighborly overtures have blossomed into an innovative collaboration in the fight against SARS.
"At the time, I was thinking about how to utilize my specialty to try to create some new vaccines because already there were some SARS candidate vaccines that had been reported," said Huang. "We shared the same general interest in viral assembly and Brenda is the expert in this topic, so I approached her and said ‘how about we do something together?’ I think a common interest just merged there."
"I think a part of it is just being located in the open interactive environment at Biodesign and chatting occasionally," said Hogue. "Zhong was talking with some of my graduate students, attended some of their talks and posters, and in the process, we got a better sense of what each of our labs do."
Several members of their labs including graduate student Ariel Arndt and undergraduates Blake Larson (a SOLUR undergraduate researcher) and Jennifer Dinh in the Hogue Lab, as well as two incoming postdocs, will join forces to develop the vaccine candidates. This effort involves expertise in the fields of molecular biology, virology, biochemistry, vaccination and immunology. In addition, the research team will evaluate the effectiveness of their vaccine candidates in partnership with research associate professor Dale Barnard in the Institute for Antiviral Research at Utah State University as part of ongoing NIH funded contract to evaluate all types of therapies in SARS-CoV animal models.
The team’s ultimate goal is to design their vaccine candidates for intranasal delivery. The research duo aims to complete major research milestones from the two-year project by 2010.
"In a broader sense, if this works for SARS, there is the possibility of targeting other virus receptor binding domains," said Hogue. "It has the potential for use as a model vaccine platform for other respiratory diseases."
