Potential method of strengthening TB vaccine discovered
EDINBURG (March 9, 2009) – New research may have uncovered a strategy for strengthening the only vaccine available today for protection against tuberculosis.
The vaccine is prepared from a strain of the weakened bovine tuberculosis bacterium. Both the human and bovine pathogens have evasive mechanisms that prevent a stronger immune response. The researchers found ways to overcome these mechanisms and strengthen the immune response in mice.
The finding appeared in the March issue of the journal Nature Medicine. Subramanian Dhandayuthapani, Ph.D., a microbiologist with The University of Texas Health Science Center at San Antonio who is widely known as Dr. Pani, collaborated on the study with researchers from The University of Texas Health Science Center at Houston and Baylor College of Medicine.
Dr. Pani works in Edinburg at the Medical Research Division of San Antonio Health Science Center’s Regional Academic Health Center (RAHC).
Tuberculosis (TB) is a global scourge. An estimated one in three people worldwide carries the TB pathogen, according to the World Health Organization. Eight million people develop active TB disease each year, and 1.6 million die. The airborne disease is highly contagious and usually attacks the lungs, although it can affect other organs.
Poverty, limited access to health care and a mobile population have led to higher levels of TB along the Texas-Mexico border than in most other parts of the United States.
“This research, I believe, makes significant contributions to the prevention of TB worldwide,” said Leonel Vela, M.D., M.P.H., regional dean of the RAHC. “And it really points to the level and quality of research occurring at the Edinburg RAHC that has implications for the population here in the Rio Grande Valley, where rates of TB are disproportionately high compared with the rest of the country.”
The TB vaccine, called bacille Calmette-Guérin (BCG), was first tested in humans in 1921 and remains the only vaccine in use for TB today. But its effectiveness is highly variable. It is generally shown to be more effective in children; however, studies of pulmonary TB, which is more common in adolescents and adults, have shown the vaccine to be effective in anywhere from 80 percent of cases to none at all.
The World Health Organization describes BCG as the most controversial vaccine in widespread use today. It is generally not recommended for use in the United States.
Tuberculosis, including the weakened bovine strain used in the BCG vaccine, hides in cells so its antigens – the substances that cause an immune system to produce antibodies to fight a disease – are concealed.
The researchers used rapamycin, a drug often used to prevent the rejection of organ and bone marrow transplants by the body, to induce a process called autophagy, in which a cell consumes its own components. This process prompted a particular TB antigen to move into pathways where it could be recognized by the immune system. As a result, the immune response was strengthened.
The group also discovered that antigen presentation can be further enhanced by introducing a genetically modified form of BCG that overproduces a TB antigen called Antigen85. Injecting this recombinant BCG into mice led to better protection against TB than was seen when mice were injected with the standard BCG vaccine.
Researchers speculate that their findings might have implications not just for BCG but also for other vaccines.
“Now we have the mechanism,” Dr. Pani said. “We know exactly how we can enhance the antigen presentation.”
Thomas J. Slaga, Ph.D., interim director of the Edinburg RAHC, called Dr. Pani’s collaboration with the Houston Health Science Center and Baylor “very significant for the Valley.”
“It shows the development of the research program at the Edinburg RAHC – that we have the caliber of people to turn it into an outstanding research institute,” Dr. Slaga said.
Dr. Pani collaborated on the research with Chinnaswamy Jagannath, Ph.D.; Robert L. Hunter, M.D., Ph.D.; and Devin Lindsey, M.S., from The University of Texas Health Science Center at Houston; and with N. Tony Eissa, M.D., and Yi Xu, Ph.D., from the Baylor College of Medicine.
The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $668 million, the Health Science Center is the chief catalyst for the $16.3 billion biosciences and health care sector in San Antonio’s economy. The Health Science Center has had an estimated $36 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 24,000 graduates (physicians, dentists, nurses, scientists and other health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, dentistry and many other fields. For more information, visit www.uthscsa.edu.