TB remains one of the world's major killer diseases, causing TB disease in 9.6 million people and 1.5 million deaths in 2014. The only available vaccine, Bacillus Calmette-Guérin (BCG), works well (estimated 50% effective) to prevent severe disease in children but is very variable (0% to 80% effective) in how well it protects against lung disease, particularly in countries where TB is most common.
While BCG is one of the safest and most widely used vaccines worldwide, there is one key issue: It is currently very difficult to determine whether it will work or not. This also makes it really hard to determine if any new vaccines might work.
For many vaccines, medics and scientists can use what are called immune correlates or biomarkers, typically in the blood, which can be measured to determine whether a vaccine has successfully induced immunity. Not only are these correlates useful in measuring the success of existing vaccination programmes, they are also invaluable in assessing whether potential new vaccines could be effective.
With a pressing need for a TB vaccine that is more effective than BCG, a research team studied immune responses in infants in South Africa who were taking part in a TB vaccine trial.
'The team carried out tests for twenty-two possible factors. One - levels of activated HLA-DR+CD4+ T-cells - was linked to higher TB disease risk. Meanwhile, BCG-specific Interferon-gamma secreting T-cells indicated lower TB risk, with higher levels of these cells directly linked to greater reduction of the risk of TB.
Antibodies to a TB protein, Ag85A, were also identified as a possible correlate. Higher levels of Ag85A antibody were associated with lower TB risk. However, the team cautions that other environmental and disease factors could also cause Ag85A antibody levels to rise and so there may not be a direct link between the antibody and TB risk.
The author said: 'These are useful results which ideally would now be confirmed in further trials. They show that antigen-specific T cells are important in protection against TB, but that activated T cells increase the risk".
Another author, said: "For the first time we have some evidence of how BCG might work, and also what could block it from working. Although there is still much work to do, these findings may bring us a step closer to developing a more effective vaccine for TB."
Biomarker discovery in TB vaccine treated infants
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