Tuberculosis

Strategies for new vaccine development

On the path of a leading killer

Tuberculosis—one of the most harmful human infectious diseases—kills two million people worldwide every year. According to the World Health Organization, one third of the world’s population is infected with Mycobacterium tuberculosis, causative agent of the illness, with 8 million cases diagnosed annually. New infections are occurring at a rate of about one per second, with a growing percentage of recent cases showing multi-drug resistance.  

We are working on several active fronts to combat tuberculosis, a scourge that has persisted throughout recorded history.  While the challenges are daunting, significant progress is being made. Understanding the subtle mechanisms by which M. tuberculosis bacteria causes TB is one of the central goals of the Institute’s Center for Infectious Diseases and Vaccinology.



M. tuberculosis is highly contagious, but to contract the disease, two stages are required: first, an individual must be infected with the bacterium; second, the infection must progress to the disease stage. Transmission occurs through the dispersal of nasal droplets from an infected carrier. The ingestion of a single M. tuberculosis bacterium is enough to cause infection, though only about one in ten latent infections will develop into active tuberculosis. About half of these patients will die if the infection is left untreated.

While the body’s natural defenses can usually stave off the activation of tuberculosis, the bacteria, once ingested, can remain viable, persisting in a dormant state. Should the body’s immune system weaken for any reason, the mycobacteria can spread and then attack. Those most vulnerable to tuberculosis include people under immunosuppressant therapy and anyone suffering from immune diseases, particularly HIV. For individuals co-infected with TB and HIV, tuberculosis is now the leading cause of death, and is responsible for 13 percent of all AIDS fatalities worldwide.

Research has focused on understanding the specific genes that permit tuberculosis bacteria to survive and grow within human macrophages—specialized cells whose role it is to seek out and destroy infectious bacterial invaders. This essential topic of research is being investigated by means of a powerful approach developed by Josephine Clark-Curtiss and her colleagues, known as selective capture of transcribed sequences, or SCOTS. The strategy is able to identify gene expression patterns in bacteria present during natural infection without specialized genetic techniques.

Tuberculosis is notoriously difficult to treat, requiring a lengthy regimen of drugs, often unavailable in areas where they are most needed—tubercular hot spots throughout the developing world. One of the most exciting branches of research at Biodesign is aimed at the development of a safe, low cost vaccine. Although an existing vaccine known as BCG has shown effectiveness in children, it does not confer lifelong immunity, leaving young adults particularly vulnerable. A novel strategy under development at Biodesign involves the use of an attenuated Salmonella vaccine carrier, capable of generating a powerful, sustained immune response to infectious bacilli.  

This cooperative, multidisciplinary research is advancing medical science step-by- step toward the goal of a tubercular-free world.

Collaborators:
  • University of Maryland ’s Center for Vaccine Development
  • St. George's Hospital’s Dept. of Infectious Diseases (London, England)
  • The Council for Scientific and Industrial Research in Pretoria (S. Africa)
  • Mapp Biopharmaceuticals, Inc. (San Diego)
  • Baylor College of Medicine’s Virology Department  (Houston, TX)
  • University of Rochester’s Infectious Disease Unit  (New York)
  • Roswell Park Cancer Institute’s Department of Molecular Immunology (Buffalo, NY)
  • National Institute of Infectious Diseases’ Department of Virology II (Tokyo, Japan)
  • University of Alabama at Birmingham (Birmingham, AL)
  • Tufts University (Boston, Massachusetts)
  • International Vaccine Institute (Seoul, Korea)
  • Saint Louis University
  • University of Adelaide (South Australia)
  • Pusan National University, (Pusan Republic of Korea)
  • Duke University, (North Carolina)
  • University of Melbourne (Melbourne, Australia)
  • University of Kentucky (Lexington, Kentucky)
  • Washington University (St. Louis, Missouri)