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UT, Georgia, Canadian scientists working to develop vaccine for two bacterial diseases |
| By
Jim Winkler |
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Dec 2, 2008
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A University of Toledo infectious disease researcher is teaming with scientists from the University of Calgary and the University of Georgia to develop a vaccine against two serious bacterial diseases.
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| Developing a vaccine is a complex endeavor that requires a multifacted approach, according to Dr. Mark Wooten, who is teaming with scientists from the universities of Calgary and Georgia to develop a vaccine for two closely related diseases, glanders and melioidosis. |
Dr. Mark Wooten, associate professor of medical microbiology and immunology, is joining Dr. Eric Lafontaine, a former Medical College of Ohio microbiologist who is now at UGA’s College of Veterinary Medicine, and Calgary microbiologist Dr. Donald Woods, who was awarded a $1.7 million grant from the National Institutes of Health to develop vaccines against two highly infectious diseases — glanders and melioidosis — that can be spread between animals and humans with fatal results.
Caused by the bacterium
Burkholderia mallei, glanders typically infects horses, mules and donkeys, although it also can be transmitted to humans. Historically, the bacteria were used as an early form of germ warfare — it was allegedly spread among horse herds during the Civil War and World War I in an attempt to disrupt an army’s ability to effectively move troops, artillery and supplies. Eliminated from the United States in the early 1900s thanks to good veterinary practices, the disease is still found in certain areas of the world.
Closely related to glanders, melioidosis is caused by
Burkholderia pseudomallei and is found ubiquitously in the soil and water throughout India and southeast Asian countries such as Thailand and Cambodia, and more recently in Central America and the Bahamas, which have become active regions for disease transmission.
Entering the body through the skin, by inhalation, or by ingesting contaminated food or water,
B. pseudomallei leads to illnesses ranging from uncomplicated skin infections to more serious, life-threatening diseases such as bloodstream infections and pneumonia. The disease is particularly lethal in people with diabetes, kidney disease or weak immune systems.
Because the bacteria causing these illnesses are so similar, it is hoped that a single vaccine would likely be effective for both, according to Wooten.
Woods, considered one of the world’s top authorities on the two diseases, has discovered that both bacteria are encased by a protective capsule made of carbohydrates that allow the microbes to evade the immune system’s specialized cells that normally degrade disease-causing bacteria, as well as to resist antibiotics and hide out in the lymph nodes and other organs where they can remain infectious for decades after treatment ends.
Today, melioidois cases are beginning to appear among Vietnam War veterans who acquired the persistent bacteria during the war, but are only now developing disease as their immune systems break down with age.
“The bugs,” Wooten explained, “make a big carbohydrate capsule layer on their outside that makes them look very uninteresting to our immune cells, so that once they eat the bacteria they do not become appropriately stimulated to clear the infection, and the bugs are able to survive to later escape and cause severe disease.”
Embedded within the capsule are proteins that allow them to adhere to host tissues and make the bacteria more virulent.
In independent studies, Woods, Lafontaine and Wooten have described important protective properties of the carbohydrate capsule and unraveled some of the genetic machinery of the bacteria, including the identification of seven outer membrane proteins on the bacteria that could be candidate targets for new vaccines.
To get the immune system to recognize the carbohydrate capsule on the bacteria and respond appropriately to clear the infection, the researchers will link the capsular material with seven proteins on the outer membranes of the two bacteria and see if these more complex vaccines stimulate a protective immune response.
Woods has developed laboratory techniques to make large amounts of the carbohydrates for the capsules, while Lafountaine, using recombinant DNA techniques, will produce recombinant forms of the outer membrane proteins that can be purified.
Doses of the seven different conjugate vaccines will be administered to mice, the model for
B. pseudomallei infection, and horses, the model for
B. mallei infection, to determine whether they can protect from disease development.
Wooten will examine and define the animals’ immune system response to each of these seven vaccines — the response of antibodies, phagocytes, helper and cytotoxic T-cells, cytokines and other patterns that are a part of the immune system that remembers previous encounters with bacteria and viruses, and subsequently mounts a quick and vigorous defense if they ever encounter the same germs again.
“By comparing the patterns of immune responses to vaccines that work versus those vaccines that are ineffective, we can determine which immune mediators are important for protection from these bacteria and figure out which branches of the immune response we need to tweak to make the best vaccine,” Wooten said.
A postdoctoral fellow, Dr. Mike Woodman from the University of Kentucky, will join Wooten’s lab next month to help in the project.
“We’re going to figure this out,” Wooten said. “It’s going to be challenging, but fun work. We have a ton of ideas and projects for these bugs.”
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