A third of the world population is latently infected with Mycobacterium tuberculosis and many cases of active tuberculosis arise from latent bacilli reactivation. Thus, it is important to design new vaccines to prevent reactivation. Using an experimental model of chronic tuberculosis in B6D2F1 mice, we observed constant expression of Rv1759c antigen, a member of the PE_PGRS gene family, on the cell wall of phagocytosed mycobacteria by activated macrophages located in lung granulomas. This antigen induced production of IFN-gamma after stimulation of cell suspensions from mediastinal lymph nodes. It was notorius that chronic infected mice immunized with this antigen and treated with corticosterone to induce reactivation showed not change in colony forming units (CFU), compared with the significant bacilli increase in non-vaccinated mice treated with corticosterone. These results suggest that this antigen could play an important role in the immune response that maintains latent infection, and could therefore, be a good candidate as a new subunit vaccine to prevent disease reactivation.