Protein find could offer new candidate for TB vaccine
22 March 2011
TB is caused by the bacterium Mycobacterium tuberculosis (MTB), which infects the lungs and spreads through the air as a result of coughing. The BCG vaccine derives from the Mycobacterium bovis bacterium, which infects cattle and is closely related to MTB.
"Despite most of the world's population having had a BCG vaccination, there are still nine million new cases of TB every year," said senior author Professor Ajit Lalvani, from the National Heart and Lung Institute at Imperial College London. "So we urgently need to develop a more effective vaccine for TB."
In the new study, funded by the Wellcome Trust, 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 produced by the TB bacterium but is not present in 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 team 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. They 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 reacted to the protein, showing that the response is specific to the MTB bacteria. Further experiments revealed that this is because the BCG vaccine, based on the cattle bacterium, lacks genes that are needed to produce EspC.
As the immune reaction to the protein can be detected in TB-infected people but not in uninfected people who have had the BCG vaccine, the protein could also prove useful as a diagnostic tool. The currently used 'skin-prick' test, or Mantoux test, is unable to do this because the protein used in the test is present in both the MTB bacteria and the BCG vaccine.
Professor Lalvani added: "We've shown that EspC, which is secreted by the bacterium, provokes a very strong immune response, and is also highly specific to MTB. This makes it an extremely promising candidate for a new TB vaccine that could stimulate broader and stronger immunity than BCG. Surprisingly, our results also show that this molecule could underpin next-generation diagnostic blood tests that can rapidly detect latent TB infection."
The study was published online last week in 'Proceedings of the National Academy of Sciences'.
Image: A positive ‘skin-prick’ test, or Mantoux test. Credit: Wellcome Images.
Reference
Millington K et al. EspC is a highly immunodominant E1-dependent secreted antigen specific for Mycobacterium tuberculosis infection. PNAS [epub ahead of print].
