For the first time, researchers have discovered some evidence on how the tuberculosis (TB) vaccine, Bacillus Calmette-Guérin (BCG), may work. Among their findings they observed how activated T cells can increase the risk of TB, and how biomarkers and correlates may cause immunity in some patients.  

Researchers from Oxford University and the University of Cape Town studied immune responses in infants in South Africa in order to identify biomarkers, aiding the eventual development of a more effective vaccination.

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They found that levels of activated HLA-DR+CD4+ T-cells were linked to higher TB disease risk, while BCG-specific interferon-gamma secreting T-cells indicated lower TB risk. Higher levels of these gamma secreting T-cells were associated with greater risk reduction of TB.

Ag85A was identified as an antibody to a TB protein and a possible correlate. Individuals with a higher level of Ag85A were recognized as having a lower risk of TB. However, the authors noted that other environmental and disease factors may also cause Ag85A antibody levels to rise and so there may not be a direct link between the antibody and TB risk.

“[These results] show that antigen-specific T cells are important in protection against TB, but that activated T cells increase the risk,” said Professor Helen McShane, one of the studies lead authors. “These are useful results which ideally would now be confirmed in further trials.”

The number of TB related deaths in 2014 was 1.5 million worldwide. The BCG vaccine is proven to be effective in approximately 50% of cases to prevent severe disease in children. However, it is extremely variable – 0% to 80% effective – in how well it protects against lung disease.

“The findings [from this study] provide important clues about the type of immunity TB vaccines should elicit, and bring us closer to our vision, a world without TB,” said Dr. Tom Scriba from the South African Tuberculosis Vaccine Initiative.

The research team is currently working on developing a new TB vaccine.

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