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Tuberculosis research under FP6


Approximately eight million people develop active tuberculosis (TB) each year, with two million dying from the disease. In addition, it is estimated that up to two billion people have been infected with the causative agent, Mycobacterium tuberculosis. As M. tuberculosis is still one of mankind's most successful pathogens, it is imperative to make a well-focused effort to challenge its grasp on humankind.

In many regions, the M. tuberculosis strains have become resistant to most of the drugs currently being used to control the growth and spread of this pathogen. The famous BCG vaccine was designed to control tuberculosis. However, analysis of the effect of BCG vaccination in human populations has revealed controversial results. The vaccine strain seems to be able to raise protective immunity in children but the results with adult populations are not adequate. New, more efficient, vaccine strains are needed.

The TB projects, funded under the Sixth Framework Programme (FP6), aim at developing new vaccines, more efficient drugs and better diagnostic tools against tuberculosis. In TB control, long treatment duration and drug resistance among M. tuberculosis strains seem to be obstacles that cannot easily be overcome. New technological tools, utilisation of information from genomics and identification of new targets involving, for example, persistence related factors, are seen as effective measures in TB research. The establishment of production technologies for lead compounds into new anti-TB drugs is also an essential component of the projects strategy.

In the context of the Fifth Framework Programme (FP5), several promising new vaccine strategies were developed. The aims of the FP6 integrated project (IP) for tuberculosis vaccine is to: integrate European efforts towards the development of these vaccine candidates; forward these to small-scale, phase 1, human clinical trials and; liaise with other consortia of vaccine development and with the European and Developing Countries Clinical Trials Partnership (EDCTP) so as to enable further large clinical trials in Africa.

Smaller projects in the area utilise expression libraries representing the whole M. tuberculosis genome in order to perform a genome-wide identification of novel target proteins or use entire expressed genomes of both the host and the pathogen during the infection to look at the cellular immune response to mycobacterial proteins.

Illustration for tuberculosis

The integrated project for new TB drug development has a comprehensive selection of potential and validated targets in addition to novel proprietary anti-TB agents in its development pipeline. The aims of the project are to develop new drugs with the highly desirable properties of activity against persistent bacteria, inhibition of new target classes and activity against multidrug resistant TB. Other projects concentrate on the diagnosis of drug resistant tuberculosis and on the diversity of TB strains, as well as on the development of protocols capable of identifying novel drug-binding sites and drug-protein complexes.

In both the second and fourth call devoted to this area, small-scale innovative high-risk projects were sought which involved approaches going beyond the current state-of-the-art in the development of interventions for tuberculosis. These include a project on TB drug development looking at persistence-related drug targets, a project focused on mechanisms involved in neonatal immune responses to mycobacteria, and projects concentrating on targets that are related to persistence or to lipid metabolism of M. tuberculosis. Projects on diagnostics target detection of drug resistant tuberculosis and application of technology suitable for research poor settings.

Tuberculosis continues to present great challenges to vaccine and drug development. These challenges are likely to be met through excellent project portfolios funded under FP6. Results will be achieved by combining fundamental research in genomics and in the immune response to mycobacterial infection with high-throughput screening and empirical testing of novel candidates in animal models. Investigation of the immunogenicity and efficacy of selected candidates in human trials represents one of the most urgent challenges for the future.

Hannu Lång
Scientific Officer, Tuberculosis

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