Scientists have discovered a protein secreted by tuberculosis (TB) bacteria that could be a promising new vaccine candidate, as reported in Proceedings of the National Academy of Sciences. The protein could also be used to improve diagnosis of TB.
There are nine 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.
In the new study, scientists identified a protein, called EspC, that 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, which was funded by the Wellcome Trust, looked at how the immune system responded to EspC in 45 people with active TB, 27 people with latent TB infection, and 27 uninfected BCG-vaccinated controls. It found that EspC elicited immune responses at least as strongly as other proteins known to be targeted by the immune system in people with active and latent TB infection. Only two out of 27 BCG-vaccinated controls responded to the antigen, demonstrating the specificity of the response. Further experiments revealed that this is because the TB vaccine lacks genes that are needed to secrete EspC.
Source: Imperial College London