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Immune System Quirk Could Lead to Effective Tularemia Vaccine

PITTSBURGH, Oct. 22, 2009 – Immunologists at the University of Pittsburgh School of Medicine and Children’s Hospital of Pittsburgh of UPMC have found a unique quirk in the way the immune system fends off bacteria called Francisella tularensis, which could lead to vaccines that are better able to prevent tularemia infection of the lungs. Their findings were published today in the early, online version of Immunity.

F. tularensis is an intracellular pathogen that infects cells in the lungs called macrophages, explained senior author Shabaana A. Khader, Ph.D., assistant professor of pediatrics and immunology at the School of Medicine and an immunologist at Children’s Hospital. Until now, scientists thought that eliciting a strong immune response to clear the infection would only require activation of a cytokine protein called interferon gamma (IFN-gamma). But that’s not true for F. tularensis as it is for other intracellular bacteria, such as the TB-causing Mycobacterium tuberculosis.

“Our lab experiments show that in order to activate IFN-gamma in pulmonary tularemia, it is necessary to first induce production of another cytokine called interleukin-17,” Dr. Khader explained. “So if we want to make an effective vaccine against tularemia, we must target ways to boost IL-17.”

According to the U.S. Centers for Disease Control and Prevention (CDC), the virulent strain of tularemia commonly causes infection in wild animals, and about 200 human cases are reported annually in the United States. It can be spread through the bites of infected insects, the handling of sick or dead animals, eating or drinking bacteria-contaminated food or water, or by inhalation of airborne bacteria. Antibiotic treatment is effective.

Although not transmissible from person to person, it is highly infectious. Because only a small amount of the virulent bacteria can cause disease and spread through the air to cause severe respiratory illness, it could be a candidate for a bioweapon, the CDC has noted. A safe, lab-adapted live vaccine strain was used in Dr. Khader’s study.

Dr. Khader’s team will continue its work by studying how to target lung IL-17 responses to develop vaccine strategies for pulmonary tularemia.

Study authors are from Children’s Hospital, the University of Pittsburgh School of Medicine, University of Rochester Medical Center, Washington University School of Medicine and the University of Tokyo.

The research was funded with grants from the National Institutes of Health and Children’s Hospital.

As one of the nation’s leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to preliminary data for fiscal year 2008. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region’s economy. For more information about the School of Medicine, see www.medschool.pitt.edu.

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