Mycobacterium tuberculosis causes tuberculosis and is one of the main killers among infectious pathogens in the world, and an important factor that sustain poverty in developing countries. Applied research for development of new vaccines is therefore need ed. Transmission of tuberculosis (TB) is mainly effected by patients with reactivated TB. The research program aims at developing a vaccine to prevent reactivation of TB. A twofold strategy will be used. I. To have an extensive antigen discovery and evalu ation program to extend the possibilities to target antigens of M. tuberculosis for developing novel subunit vaccines to boost protective immune responses in a postexposure setting. II. To reestablish the already developed mouse models for slowly progress ive and latent TB into models that can be used to test vaccines against reactivation of TB. Researchers in Bergen have recently discovered a large number of novel secreted proteins in a unique M. tuberculosis culture filtrate. A research programme to disc over and assess the value of novel secreted proteins is the first goal of this proposal. Selected proteins identified by proteomics will be further characterized for immunogenicity. Synthetic peptides and recombinant protein purified from M. smegmatis wil l be used to test the immunogenic potential of these proteins. Antigen-specific cellular immune responses in patients with TB, healthy individuals with latent TB infection, BCG vaccinated healthy individuals and unvaccinated controls will be tested. Mouse models for latent TB and slowly progressive TB developed in Bergen will be reestablished to evaluate the immunogenic potential of novel antigens.