Tuberculosis (TB) is an airborne bacterial infection caused by Mycobacterium tuberculosis. TB primarily attacks the lung, causing cough, fever, and weight loss, but microbes can travel via the bloodstream to tissues such as bone or kidney. And, if they lodge in the meninges, or membranes, that surround brain, they can cause life-threatening meningitis.
Fortunately, many people who contract TB mount a successful immune response leading to disease resolution. In others, however, the disease remains in a latent rather than an active state held in check by the patient’s own immune system, and sometimes by antibiotic treatment. In a small number of patients, however, the microbe can be re-activated if the immune system is weakened.
Currently, a TB vaccine known as BCG is used to vaccinate children living in countries with a high TB incidence. BCG is fairly effective in preventing TB-related childhood meningitis, but it is not used in the U.S., as it is minimally effective against adult lung disease. This limitation, coupled with the emergence of multi-drug-resistant strains, puts TB near the top of the list in the search for vaccines to prevent worldwide health problems.
LJI scientist Alessandro Sette is one of four recipients nationwide of a Human Immune Profiling Consortium (HIPC) grant established by the National Institutes of Allergy and Infectious Disease to characterize the immune response to TB bacteria (this project will also address immune responses dengue virus). In this effort, he is examining T cell responses in patients with latent TB infections and asking how to stop their progression to a more active form of the disease.
Thus far, his studies suggest that progression to the active disease is more likely to be halted if a vaccine stimulates strong, protective T cell responses. Teaming up with LJI colleagues Pandurangan Vijayanand, Ph.D., and Bjoern Peters, Ph.D., Sette is applying unbiased methods to identify T cell molecular attributes or “signatures” associated with disease protection. For example, if one could identify a discrete molecular feature of the TB microbe (called an epitope) that stimulated a protective T cell response, that element could be incorporated into a new experimental vaccine to elicit that response.