In an effort to drive innovation in tuberculosis (TB) research, the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) has selected four sites, including one led by Emory University and collaborating institutions, for a Tuberculosis Research Units (TBRU) network. The NIH will award the Emory-led TBRU approximately $18.7 million over seven years.
Tuberculosis (TB) is an enormous global public health problem. According to the World Health Organization, about one-third of the world’s population carries latent TB bacteria. In 2013, an estimated nine million people became ill with active TB and 1.5 million died from the disease. More than 500,000 children developed TB in 2013 and 80,000 died from the infection, according to WHO.
The four TBRUs will work together to examine how Mycobacterium tuberculosis(Mtb), the organism that causes TB, interacts with the human host and the immune system to cause disease, with the aim of improving diagnosis, prevention, vaccines and therapies.
Principal investigator of the Emory-led TBRU is Henry Blumberg, MD, professor of medicine in the Division of Infectious Diseases at Emory University School of Medicine and professor of epidemiology and global health in the Rollins School of Public Health. Co-principal investigator is Joel Ernst, MD, of New York University. Their project is named "Role of Antigen-Specific T Cell Responses in the Control of TB."
Although infection with the tuberculosis bacterium (Mtb) causes active disease in only a fraction of infected people, latent TB can reactivate and progress to active, transmissible and potentially fatal disease.
"The differences in immune responses in those who remain well and those who become ill are not well understood," says Blumberg. "Our research team will apply innovative immunology research concepts and technologies to explain the different risk levels and outcomes of latent infection. We believe our discoveries can help provide new tools to improve public health efforts and to guide TB vaccine development."
The goal of the Emory-led TBRU is to help eliminate TB through a comprehensive understanding of antigen-specific T cell responses and their relationship to distinct outcomes of Mtb infection. Their primary hypothesis is that latent TB infection is a spectrum of three main immune states: (1) past, but cleared infection; (2) stable infection with a low risk of progression to active disease; or (3) infection with a high risk of progression to active TB disease.
These differences, they believe, correlate with differences in antigen-specific T cell responses that contribute to the outcome of infection with Mtb and can be detected through sophisticated analysis of blood.
By identifying individuals with latent TB infection at greatest risk for progression to active TB, prevention strategies could be used to target those at highest risk both in areas with high rates of TB infection (usually low and middle income countries) where treating persons with latent TB infection has been impractical because of limited resources and risk for reinfection, as well as high income countries such as the U.S. as part of public health efforts to control and eliminate TB.
The researchers will use state-of-the-art concepts and technologies to define the spectrum of antigen-specific recognition of T cells in Mtb infection and develop tools to identify people at highest risk of progressing to active TB. They also will identify T cell responses associated with immunity to Mtb to guide development of effective TB vaccines, and study the impact of re-exposure and reinfection on antigen specific T cell responses and progression to active TB.
In addition to Emory and NYU, collaborators will include investigators at the U.S. Centers for Disease Control and Prevention (CDC), the Kenya Medical Research Institute (KEMRI)/CDC, DeKalb County (Georgia) Board of Health, La Jolla Institute of Allergy and Immunology, and Aeras. Studies of TB in nonhuman primates will be done by experts at Emory’s Yerkes National Primate Research Center and the Tulane National Primate Research Center.
In addition to Drs. Henry Blumberg and Joel Ernst, key TBRU team members include Drs. Rafi Ahmed, John Altman, Cheryl Day, Neel Gandhi, Jyothi Rengarajan, Francois Villinger, and Lance Waller at Emory, as well as Dr. Deepak Kaushal at Tulane, Dr. Kevin Cain at KEMRI/CDC, Dr. Sarita Shah at CDC (Atlanta), Dr. Alawode Oladele at the DeKalb County Board of Health, and Dr. Alex Sette at the La Jolla Institute of Allergy and Immunology.
The NIAID named three other new TBRUs: Boston Medical Center, Boston, with co-investigators at Rutgers University; Brigham and Women’s Hospital, Boston, with co-investigators at Harvard School of Public Health; and Weill Cornell Medical College, New York City, with co-investigators at Sloan Kettering Institute for Cancer Research.
For more information, see the NIH press release.