Veterinary College Researcher Awarded $1 Million Military Grant To Develop Bioterror Vaccine

A bacteriologist in the Virginia-Maryland Regional College of Veterinary Medicine has been awarded a $1.06 million grant from the U.S. Army to develop a vaccine for tularemia.

Thomas J. Inzana, the Tyler J. and Francis F. Young Professor of Bacteriology, along with his research team in the college's Center for Molecular Medicine and Infectious Diseases have begun a four-year program designed to develop a vaccine and diagnostic test for tularemia, which is commonly known as "rabbit fever." The etiologic agent of tularemia is Francisella tularensis, which the Centers For Disease Control (CDC) in Atlanta classifies as a Category A bioterrorism agent.

Tularemia is an infection characterized by ulcers, swollen glands, fever, and flu-like symptoms. The organism can spread through the blood and lymphatic systems to infect the respiratory tract, where it can cause more serious health problems. Pneumonic tularemia may have about a 30 percent mortality rate, according to Inzana.

While not uncommon in wildlife throughout the United States, Inzana says, it is a relatively rare disease in people. Only about 100-200 cases of tularemia in humans are reported every year, Inzana said. The bacteria are transmitted to humans and animals by ticks and biting flies, or can be ingested by wildlife from drinking water. Humans are also infected through minor cuts or abrasions in the hands by handling infected animals.

The military is concerned about F. tularensis because of its heartiness and its virulence. Whereas about 10,000 Bacillus anthracis (anthrax) spores are required to cause disease, only about 10 F. tularensis cells are required to cause disease, according to Inzana. The organism could conceivably be aerosolized and used as a bioterrorism agent at home or abroad; hence, the military interest. A World Health Organization Committee estimated that aerosol dispersal of 50 kilograms of virulent F. tularensis over a city of 5 million people would result in 250,000 inhabitants becoming seriously infected, including 19,000 deaths.

One aspect of F. tularensis that makes it dangerous is its ability to resist host defenses, Inzana says. Unlike many bacteria, F. tularensis has the ability to survive inside some of the front-line defenders of the body's immune system. As phagocytic cells such as macrophages rush to attack and consume the invading pathogens, F. tularensis actually uses the macrophage as a home and multiplies within it.

While scientists do not yet know much about the biology of the organism, they do know that it has a capsule-like substance on its surface. Inzana, who recently developed and patented a vaccine for swine pleuropneumonia by mutating the DNA required for capsule synthesis by Actinobacillus pleuropneumoniae, and selecting for a non-capsulated vaccine strain, plans to apply his expertise in bacterial carbohydrate antigens to the new vaccine and diagnostic test development program.

His research team will isolate and characterize both the capsule and the outer membrane proteins that enable the organism to survive inside the macrophage. The key to creating an effective vaccine will be their ability to identify and stimulate the production of proteins that stimulate T-cells of the cellular immune system. It is hoped that antibodies to the capsule will help to clear the bacteria that are not yet in phagocytic cells, and that T cells of the cellular immune system will kill the cells harboring the bacteria.

In another aspect of the project, Inzana is working with Anbo Wang and Kirstie Cooper in the College of Engineering's Center for Photonics Technology on a project that will develop photonic-based bio-sensors to detect the F. tularensis capsule or DNA in the field. Ultimately, that research could lead to the development of rapid pathogen sensing biosensors that could detect multiple pathogens on the battlefield.

Inzana is a noted molecular microbiologist who has generated $4 million in extramural funding and been awarded three patents for intellectual properties arising out of research that has led to the development of vaccines for economically important agricultural diseases.

A former director of the Center for Molecular Medicine and Infectious Diseases, Inzana also serves as Director of Clinical Microbiology in the Veterinary Teaching Hospital and conducts teaching, service, and research through his appointment as a professor in the Department of Biomedical Sciences and Pathobiology. He is a diplomate of the American Board of Medical Microbiology and a Fellow of the American Academy of Microbiology.