A breakthrough strategy to improve the effectiveness of the only tuberculosis vaccine approved for humans provided superior protection against the deadly disease in a pre-clinical test, report scientists at The University of Texas Health Science Center at Houston in Nature Medicine 's Advance Online Publication March 1.
Their findings resulted from more than 6 years of research funded by the National Institutes of Health (NIH).
Bacille Calmette-Guérin (BCG) provides only partial protection against tuberculosis (TB) in children and is ineffective in adults. As a result, tuberculosis still kills almost 2 million people a year world wide. "An improved vaccine is widely seen as the best potential method of controlling the disease and is an urgent public health priority," said Chinnaswamy Jagannath, Ph.D., lead author and associate professor at The University of Texas Medical School at Houston.
BCG is a live but weakened form of a bacterium, M. bovis, which causes tuberculosis in cattle. It is sufficiently related to the human pathogen to stimulate production of specialized immune cells that fight off TB infection when it is injected into a person as a vaccine.
Many attempts have been made to improve the vaccine by incorporating antigens (molecular components of the bacteria) to induce a stronger immune response. However, tuberculosis and BCG have evasive mechanisms that prevent the development of stronger immune responses. Investigators at the UT Health Science Center at Houston investigated mechanisms by which BCG evades immune stimulating mechanisms and devised two means to neutralize them. The scientists used genetically-modified organisms and a drug used for organ transplantation to block BCG's evasive mechanisms, causing it to induce stronger immune responses. Research collaborator on the genetically-modified organisms project was Subramanian Dhandayuthapani, Ph.D., an assistant professor at The University of Texas Health Science Center at San Antonio's Medical Research Division in Edinburg, Texas.
This dual approach to the BCG vaccine was associated with a tenfold increase in the number of TB organisms killed and a threefold increase in the duration of protection in tests with an NIH-approved mouse model, Jagannath said.
"The breakthrough is that Dr. Jagannath has countered the ability of TB organisms to subvert immunization," said Robert L. Hunter Jr., M.D., Ph.D., one of the study's two senior authors and chair of the Department of Pathology and Laboratory Medicine at the UT Medical School at Houston.