New approach to finding TB antigens may lead to vaccine

19 November 2012

Tuberculosis, X-ray

Image: Coloured X-ray of the chest of a male patient with pulmonary tuberculosis (TB).©  GUSTOIMAGES/SCIENCE PHOTO LIBRARY

A new way of identifying antigens on the bacteria that causes tuberculosis (TB) may help in the search for a vaccine for this deadly disease.

Antigens are proteins on the cell surface of the bacteria that cause TB (Mycobacterium tuberculosis) that evoke an immune response in infected people. These TB antigens are incompletely understood, which is an obstacle in finding a vaccine against the disease.

Previous research has shown that, when there is limited oxygen available, M. Tuberculosis changes its metabolic state in the host's body - and can reactivate later when oxygen becomes available. In this  state M. Tuberculosis doesn't seem to replicate - this is known as latency and might explain the high levels of the population who are infected with TB but have no symptoms.

The researchers, led by Robert Wilkinson of the MRC's National Institute for Medical Research (NIMR; now part of the Francis Crick Institute) and the University of Cape Town, therefore decided to look into antigens on M. Tuberculosis that are related to this oxygen status.

In the lab, the scientists subjected M. Tuberculosis cell cultures to a prolonged lack of oxygen and identified a set of genes that appeared to play a role in enabling the cells to survive - called 'enduring hypoxic response' (EHR) genes. The EHR genes produced a response from T cells - immune cells that fight infections such as TB and are activated in the presence of antigens.

Out of the EHR genes, the team identified some as possible antigens. They did this by analysing a combination of data from the M. Tuberculosis genomesand information about immune cell responses from their experiments.

Professor Wilkinson explained: "This is the first evaluation of the ability of EHR genes to induce a human T cell response. We have identified novel immunodominant molecules - those which produce the strongest immune response. These could be characterised further to better understand the mechanism and importance of low oxygen conditions when TB infects people in real life (in vivo).

"Overall, our findings support the hypothesis that it is possible to predict antigens using genomic data."

He added that his team's approach may also help in the search for antigens on pathogens that cause other diseases.

Professor Wilkinson worked with colleagues in NIMR's Division of Mycobacterial Research and collaborators from Imperial College London, Cape Town and Seattle. The paper, Bioinformatic and empirical analysis of novel hypoxia-inducible targets of the human antituberculosis T cell response, was a featured article in the Journal of Immunology.

  • A new approach to discover antigens on the surface of the bacteria that causes TB, combining immune information with genomic data, may aid the search for a vaccine.
  • In 2010, there were 8.8 million cases of TB and almost 1.5 million deaths. A third of the world's population is infected with the bacteria that causes TB, called Mycobacterium tuberculosis (Mtb), but show no symptoms. These billions of infected people form a reservoir from which active TB disease can continue to develop - which is a major obstacle to getting the disease under control.
  •   Vaccines offer immunity to an infection by exposing someone to a dead or weakened form of the disease (or its cell surface antigens or toxins) and allowing their body to developed defences against it without developing the disease. This means that the next time that person encounters the same infection, their body will already be prepared to fight it off.