Study sheds light on TB vaccine efficacy
New, EU-funded research sheds light on the efficacy of orally administered tuberculosis (TB) vaccines, as compared to injected vaccines. However, writing in the journal the Proceedings of the National Academy of Sciences (PNAS), the scientists question the validity of the test most commonly used to test the effectiveness of potential vaccines. According to the World Health Organisation, over eight million new cases of TB are diagnosed every year and 1.6 million deaths from the disease, which is caused by a bacterium called Mycobacterium tuberculosis. Despite the prevalence and severity of the disease, there is still no truly effective vaccine against TB. In fact, doctors are still using the BCG (Bacillus Calmette-Guérin) vaccine which was developed back in 1921 by the French scientists Albert Calmette and Camille Guérin. The BCG is based on the bacteria which cause bovine TB. While the BCG is effective at preventing severe forms of childhood TB, it offers no protection against pulmonary tuberculosis in adults. With this in mind, researchers around the world are working on new TB vaccines which will offer better protection against this deadly disease; a number of potential vaccines are already undergoing clinical trials. However, there are still questions over the best route of administration for the vaccines; when it was first developed, the BCG was administered orally, but it is now injected into the skin. 'Our knowledge of the connection between protection and route of administration is paltry,' commented Stefan Kaufmann, Director of the Max Planck Institute for Infection Biology and one of the authors of the paper. In this latest study, scientists vaccinated some mice with an oral vaccine and others with an injected vaccine. The two routes offered comparable levels of protection against TB, although tests on the mice showed that the vaccine ended up in different tissues. After injecting the vaccine, the bacilli were found at high levels in the spleen, liver and lung, while after oral vaccination, the bacilli were concentrated in the small intestine and mesenteric lymph nodes, but not in deeper tissues. The work also raises questions about the validity of the biomarkers used to measure levels of immunity. Until recently, it was widely accepted that interferon-gamma producing CD4+ T cells played an important role in building up the protective effect of vaccines, and for this reason scientists often used them as a biomarker which could indicate the efficacy of a possible vaccine. However, the results of the study show that this biomarker may not be such a reliable indicator of immunity after all. With a number of potential vaccines entering the clinical trial stage, it is vital that scientists have access to a test which reliably indicates a vaccine's efficacy. 'Protection correlated best with rapid accumulation of specific CD8+ T cells in infected tissues,' said Professor Kaufmann. 'In contrast, the CD4+ T cells reflected the level of infection with Mycobacterium tuberculosis rather than the strength of protection.' 'Our data question the measurement of IFN-gamma secretion by CD4+ T cells and emphasise the need for new biomarkers for evaluation of tuberculosis vaccine efficacies,' the scientists conclude. EU funding for the study came from the MUVAPRED (Mucosal Vaccines for Poverty Related Diseases) project, which is financed by the Sixth Framework Programme.
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