Compositions and methods for treatment and vaccination against tuberculosis are disclosed. In one aspect the compositions provided include at least two polypeptides that contain an immunogenic portion of a M. tuberculosis antigen or at least two DNA molecules encoding such polypeptides. In a second aspect, the compositions provided include a fusion protein comprising at least two polypeptides that contain an immunogenic portion of a M. tuberculosis antigen. Such compositions may be formulated into vaccines and/or pharmaceutical compositions for immunization against M. tuberculosis infection, or may be used for the diagnosis of tuberculosis.