The Biodesign Institute at Arizona State University has been awarded a $3.2 million grant to develop a safe and effective vaccine against the disease tularemia, more commonly known as "rabbit fever." The bacterium that causes the disease, Francisella tularensis, is a potential biothreat agent against which no effective vaccine currently exists.
The Biodesign Institute's Center for Innovations in Medicine received the award for an approach that divides the research into two distinct projects. These are led by Stephen Albert Johnston, director of the Center for Innovations in Medicine, and Kathryn F. Sykes, a researcher within the center. Both are also faculty in the School of Life Sciences. Johnston was recruited to the institute in June of 2005, and the three-year award is the first major grant award for the center.
"The two projects are part of our center's commitment to improve our nation's ability to thwart biothreats," said Johnston. "They take advantage of unique technologies we have developed in our center to produce a subunit vaccine against tularemia."
Tularemia is a common bacteria found in small animals such as rodents and rabbits. People can be infected by handling sick animals, being bitten by an insect harboring the bacterium, eating or drinking contaminated food, or inhaling airborne bacteria. An exceptionally small bacterial exposure can lead to the disease.
It is the rare number of annual U.S. cases (about 200, according to the Centers for Disease Control) that makes the bacteria a worrisome bioterrorist threat. If used as a bioterrorist weapon, the bacteria would likely be made airborne for exposure by inhalation. Inhalation of tularemia leads to a form of pneumonia or systemic infection that causes high death rates if untreated.
The Johnston and Sykes projects are part of a $24.8 million consortium led by the University of New Mexico and funded by the National Institute of Allergy and Infectious Disease, a division of the National Institutes of Health. Other members of the consortium include the Cerus Corporation, Lovelace Respiratory Research Institute and the University of Texas, San Antonio.
"The funds for this research will be important in developing strategies that are not only applicable to a vaccine for F. tularensis but will also assist in defining a paradigm for developing vaccines against other emerging infections," according to Rick Lyons of the University of New Mexico Health Sciences Center.
Among the paradigms will be new screening strategies to increase the likelihood of generating an effective and safe vaccine. Candidate vaccines are currently made in two ways, one utilizing a whole pathogen approach and one employing subunit vaccines, which are made from pathogen components. The whole pathogen method creates a weakened version of the infectious agent and has been used repeatedly in the past, including the original polio vaccine.
But problems associated with whole pathogen vaccines can include severe side effects or in rare cases, the pathogen reverting back to cause a disease.
Subunit vaccines get around these problems by using only the part of the pathogen that can stimulate a protective immune response.
However, finding the correct subunit to elicit the immune response can often be a painstaking "needle in a haystack" approach. And in the case of an effective AIDS vaccine, researchers' hopes have been repeatedly dashed by subunit approaches.
The Biodesign group is mounting a two-pronged effort to identify the best subunits for a vaccine. Under Sykes' direction, they are taking advantage of the center's high-throughput gene building technology to make all the proteins of the bacterium and test them for the ability to elicit a good immune response.
The project headed by Johnston takes advantage of technology he and colleagues recently developed to measure the gene expression of bacterium in the host's lungs. They will map the gene expression during infection to detect the best genes in the pathogen to use in a vaccine. Both projects take advantage of the recently completed sequencing of the Francisella tularensis genome.
Together, the consortium will hope to deliver proof of concept for its approach and identify new vaccine leads while contributing to a better understanding of tularemia infection and host immune response.
Source: Eurekalert & others
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