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Study raises TB vaccine hopes

A newly identified protein secreted by the tuberculosis bacterium could prove effective as a vaccine against the disease, according to recently published research. Writing in the journal Proceedings of the National Academy of Sciences (PNAS), the team explain that the protein,...

A newly identified protein secreted by the tuberculosis bacterium could prove effective as a vaccine against the disease, according to recently published research. Writing in the journal Proceedings of the National Academy of Sciences (PNAS), the team explain that the protein, called EspC, could also be used to develop new diagnostic tests. Tuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis, which is spread through coughing. According to the World Health Organization (WHO), there were over 9 million new cases of TB in 2009 and 1.9 million people succumbed to the disease. TB treatment consists of a course of antibiotics that lasts several months; although arduous, this treatment is successful in some 86% of cases. There is a vaccine against TB. Called BCG ('bacillus Calmette-Guerin'), it is based on the Mycobacterium bovis bacterium that infects cattle and is closely related to M. tuberculosis. However, it does not provide comprehensive protection, and many people who have had the BCG go on to contract TB. The hunt is therefore on to find a new, more effective vaccine against the disease. Vaccines work by 'teaching' the immune system to remember certain molecules from the microbe; if and when the immune system encounters the molecules (and hence the microbe) again, it will mount a rapid immune response. The best vaccine candidates are those that elicit the strongest response from the immune system. In this study, scientists in the UK and the US discovered that a small protein called EspC provokes a stronger immune response in people infected with TB than any other known molecule. In contrast, EspC did not trigger an immune response in people who have received the BCG vaccination but have no history of TB infection. It turns out that EspC is secreted by M. tuberculosis but not by the BCG vaccine, as the BCG vaccine does not have the genes that code for the protein. According to the researchers, the fact that the BCG vaccine does not provoke an immune response means that a TB vaccine based on EspC would provide additional immunity over and above that provided by the BCG vaccine. 'Despite most of the world's population having had a BCG vaccination, there are still 9 million new cases of TB every year, so we urgently need to develop a more effective vaccine for TB,' underlined Professor Ajit Lalvani of Imperial College London in the UK. 'We've shown that EspC, which is secreted by the bacterium, provokes a very strong immune response, and is also highly specific to [M. tuberculosis]. This makes it an extremely promising candidate for a new TB vaccine that could stimulate broader and stronger immunity than BCG.' He added: 'Surprisingly, our results also show that this molecule could underpin next-generation diagnostic blood tests that can rapidly detect latent TB infection.' Currently, the basic diagnostic test for TB is the Mantoux test, in which a tiny part of the TB bug is injected into the skin. However, this test is unable to differentiate between people who have previously received the BCG vaccination and people who either have or have had TB. Because EspC does not provoke an immune reaction in people who have received the BCG vaccination, a test based on EspC would be more accurate at identifying people who have TB. The researchers arrived at their conclusions after gauging the immune response to EspC in 45 people with active TB, 27 people with latent TB (in latent TB the bacteria are present in the body but lie dormant), and 27 uninfected people who had been vaccinated with the BCG vaccine. While the immune systems of the people with active and latent TB responded strongly to EspC, only 2 of the 27 controls demonstrated an immune response to the protein. The findings come just a few days before World TB Day on 24 March. This year, among other things, the campaign focuses on the urgent need for more research into new drugs, diagnostic tools and treatments to tackle TB. In a statement, the Stop TB Partnership calls for 'an ambitious new research agenda,' and writes: 'We will not eliminate TB without a vaccine that is safe and effective in preventing the disease in people of all ages, but vaccine research is vastly underfunded. Funders need to step up their contribution to TB research today to achieve zero TB deaths tomorrow.'For more information, please visit: Wellcome Trust:http://www.wellcome.ac.ukProceedings of the National Academy of Sciences (PNAS):http://www.pnas.org World TB Day:http://www.worldtbday.org/

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