The main objective of this project is to gather several teams with complementary expertise to produce and evaluate new attenuated strains of M. tuberculosis as vaccine candidates. This project includes teams from 5 different European countries (France, Great Britain, Denmark, Belgium, and Spain) and an industrial partner (Pasteur Mérieux Serums et Vaccins) who has extensive expertise in the development of vaccines. We propose to generate attenuated strains of M. tuberculosis by disrupting genes involved in the pathogenesis capacity. Some potential targets for gene disruption have already been identified and will be deleted by allelic exchange. Other target will be identified either by random transposon mutagenesis or by homology with virulence genes of other bacteria. Induction of protection by attenuated M. tuberculosis strains will be evaluated in mouse and guinea pig models and compared with protection conferred by BCG. This project has been made possible by the construction of genetic and immunologic tools as a result of previous collaborative studies between the different teams and by the availability of sequences coming from the ongoing TB genome project. These tools will be further developed during the course of this project. They should be valuable for many other studies on mycobacteria, including the search for new diagnostic reagents and new
efficient drugs against M. tuberculosis.
Funding SchemeCSC - Cost-sharing contracts
2301 CE Leiden
2300 Kobenhavn A