To reduce the alarming number of tuberculosis deaths reported worldwide – despite a vaccine – the National Institutes of Health has awarded a five-year, $4.4 million RO1 grant to The University of Texas Health Science Center at Houston (UTHealth) to find a way to boost its effectiveness. The grant is in collaboration with Texas Biomedical Research Institute in San Antonio.
The vaccine, which has been used for nearly a century, provides only partial protection in children and is ineffective in adults, with the result that tuberculosis still kills almost 2 million people a year worldwide.
“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., one of the study’s two principal investigators and a professor of pathology and laboratory medicine at McGovern Medical School at UTHealth.
Marie-Claire Gauduin, Ph.D., associate scientist and immunologist at Texas Biomed, is also a principal investigator on this study and is collaborating with Jagannath on the project.
Jagannath and Gauduin believe they can strengthen the protective powers of the Bacille Calmette-Guérin (BCG) vaccine – named after its originators – through a twofold approach.
Vaccines work by strengthening a person’s immune system. When a tiny amount of a disease-causing bacterium is injected, the body responds by producing specialized immune cells and antibodies that can last for years to fight off the infection.
In the case of Mycobacterium tuberculosis, the protection lasts only about 10 years.
“Vaccines have had the greatest impact on human health next to clean drinking water,” Jagannath said. “Countless lives are saved each year either due to childhood or adult vaccinations.”
In earlier preclinical tests in mice involving a modified version of the BCG vaccine, Jagannath and his colleagues increased the vaccine’s bacteria-killing power tenfold and the length of its protection threefold.
Tuberculosis can be spread from person to person through the air and only a few germs need to be breathed in for a person to become infected, said Jagannath, who is a vaccine biologist with more than 35 years of experience in tuberculosis research.
People with compromised immune systems, such as those who have human immunodeficiency virus or HIV, are particularly susceptible, said Gauduin, who has more than 20 years of experience in HIV vaccine and immunology work.
The symptoms of tuberculosis can include a cough, chest pains, fever, feebleness, weight loss and night sweats. Tuberculosis is treatable, but drug resistance can happen when medicines are used inappropriately.
Jagannath and Gauduin’s twofold approach to block BCG’s evasive mechanisms involves the use of genetically modified BCG vaccine and a drug used for organ transplantation called rapamycin.
The genetically modified BCG was developed in conjunction with Subramanian Dhandayuthapani, Ph.D., associate professor of microbiology at Texas Tech Health Sciences Center El Paso. Co-investigators from UTHealth include Arshad Khan, Ph.D., Christopher R. Singh, Ph.D., and Jeffrey K. Actor, Ph.D.
Jagannath and Robert L. Hunter, M.D., Ph.D., have collaborated for two decades on tuberculosis research. Hunter is the Distinguished Chair in Molecular Pathology and chairman of pathology and laboratory medicine at McGovern Medical School.
Jagannath has written for more than 70 peer-reviewed publications including the Journal of Immunology, Nature Medicine, and Immunity. Jagannath has received a decade of support from the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health (NIH).
Actor, Jagannath and Hunter are on the faculty of The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences.
Research is supported by National Institute of Allergy and Infectious Diseases grant number (1RO1A1122070-01A1).