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Tuberculosis

Tuberculosis (TB) is a highly contagious airborne infectious disease that affects about 8 million people worldwide, causing up to 2 million deaths each year. The majority of individuals infected with Mycobacterium tuberculosis does not progress to active disease but rather contain infection within lung granulomas where M. tuberculosis can persist in a latent state. About 2 billion people worldwide are estimated to have latent TB infection (LTBI), and are at risk for reactivation to active TB disease. Immune-suppressed individuals are at increased risk for progressing to TB; this is underscored by that fact that one-quarter of the deaths in people with HIV worldwide are caused by TB.

Current treatment for Tuberculosis involves a lengthy regimen of multiple drugs over a period of 6-9 months. There also is an urgent need for new drugs to better treat emerging multi- and extensively drug resistant (MDR and XDR) strains of M. tuberculosis. The Tuberculosis Research Program at the Emory Vaccine Center (EVC) encompasses both fundamental and translational studies targeting the mechanisms of M. tuberculosis pathogenesis and host immunity to TB in animal models and humans. In addition, the Yerkes National Primate Center at Emory University accelerates the translation of EVC’s laboratory research in therapeutics and diagnostics into the clinic.  New state-of-the-art facilities for conducting TB research in Non Human Primates (NHP) at Yerkes promotes exciting new opportunities for collaborative studies between TB investigators and the well-established joint HIV/AIDS research program in NHP.

Dr. Jyothi Rengarajan’s laboratory studies how M. tuberculosis manipulates macrophage and dendritic cell function to subvert host immunity using mouse models and human cells. Using a combination of functional genomics, proteomics, microbiologic and immunologic approaches, Dr. Rengarajan and her group have identified cell-wall associated and secreted M. tuberculosis proteins that modulate innate and adaptive immune responses.  With the goal of developing new drug and immune-therapeutic targets for TB, the team is actively engaged in delineating the molecular and biochemical mechanisms. In addition, Dr. Rengarajan, in collaboration with Dr. Susan Ray and other infectious disease clinicians at Emory, is engaged in the identification of human surrogate biomarkers of latent, active and cured TB. Dr. Cheryl Day, an expert in human T cell immunology, leads the EVC’s international collaboration with the South African Tuberculosis Vaccine Initiative (SATVI), in Cape Town, South Africa. Dr. Day examines the relationship between M. tuberculosis antigen load and T cell functional capacity, as well as the regulation of M. tuberculosis-specific T cell responses in adults with LTBI and with pulmonary TB disease. Her goal is to design novel vaccination strategies and immunotherapeutic interventions in persons who develop active TB disease. The highly promising results that stem from the collaborative efforts of Drs. Day and Rengarajan provide a strong foundation for future research.

Our research program is international in scope and practice. The Joint ICGEB-Emory Vaccine Center is the direct result of our vital partnership with scientists at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in New Delhi, India, EVC faculty member Dr. Murali Krishna Kaja directs a research laboratory that bridges interactions between faculty, students and post-doctoral scientists working in both institutions. This united effort is at the forefront of research into human immunity to TB and a systems level investigation of the interactions of M. tuberculosis with immune cells. This global collaboration engages a diverse community of basic scientists and clinical investigators in the quest for improved and new TB vaccines.