Determining M. tuberculosis components to be included in vaccines
Researchers from the South African Tuberculosis Vaccine Initiative (SATVI) along with colleagues from the Center for Infectious Disease Research (CIDR), Statens Serum Institut (SSI) have published a paper titled “Antigen Availability Shapes T Cell Differentiation and Function during Tuberculosis” on 14 June 2017 in the journal, Cell Host & Microbe. The study provides important insights for determining which components of Mycobacterium tuberculosis should be included in TB vaccines as targets for the immune response. The researchers studied T cells, white blood immune cells that are critical for immunity against M. tuberculosis, that recognise two important proteins made by M. tuberculosis, ESAT-6 and Ag85B. These two proteins are included as immune response targets, or antigens, in a number of TB vaccine candidates that are currently being tested.
Although both antigens were recognised by T cells during M. tuberculosis infection of mice and humans, the T cells that recognised Ag85B were very different in function from those that recognised ESAT-6. Ag85B and ESAT-6-specific cells were also limited in their ability to do their job, namely to restrict growth of the M. tuberculosis bacterium, but for opposite reasons. Ag85B-specific T cells did not find sufficient Ag85B protein to respond to, likely because the bacterium makes only very small amounts of this protein, and therefore could not recognise cells infected with M. tuberculosis. By contrast, ESAT-6-specific cells were exposed to too much ESAT-6 protein, produced in vast amounts by the bacterium in a continuous manner throughout infection. As a consequence, much like a marathon runner who cannot sprint the entire distance, the T cells that respond to ESAT-6 become exhausted, lose function and cannot effectively fight the bacterium.
These findings pave the way for assessment of strategies to overcome these limitations in the T cell response and to assess other antigens for inclusion as immune targets in TB vaccines.
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