A team of scientists have discovered a protein secreted by tuberculosis (TB) bacteria that could be a promising candidate for a new vaccine. The protein could also be used to improve diagnosis of TB.TB is caused by the bacterium Mycobacterium tuberculosis (MTB), which infects the lungs and spreads through the air as a result of coughing. There are 9 million new cases of TB each year, killing 4,700 people a day worldwide.BCG is the only available vaccine but it is of limited effectiveness in protecting against TB. BCG derives from the Mycobacterium bovis bacterium, which infects cattle and is closely related to MTB.Vaccines work by stimulating the immune system to retain a memory of particular molecules from a microbe that will trigger a rapid immune response if the microbe is encountered later. The best candidates for vaccines are those that trigger the strongest response from the immune system.In the new study, scientists identified a protein, called EspC, which triggers a stronger immune response in people infected with the TB bacterium than any other known molecule. This protein is secreted by the TB bacterium but not by the BCG vaccine. As a result, the BCG vaccine does not induce an immune response to this protein, so deploying it as a new TB vaccine would provide additive immunity over and above that provided by BCG.The protein could also be useful as a diagnostic tool, because an immune response to it is seen in TB-infected people, but not in non-infected people who have had a BCG vaccine. Detecting immune responses to it would distinguish BCG-vaccinated people from TB-infected people, which the currently-used tuberculin skin prick test (the Mantoux test) is unable to do.The new protein could thus underpin the next-generation of immune cell-based blood tests for TB infection, known as interferon-gamma release assays (IGRAs). The researchers believe it could provide increased diagnostic sensitivity without compromising a test's ability to discriminate between BCG-vaccination and TB infection.The study has been reported in Proceedings of the National Academy of Sciences.

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