The control of chronic bacterial diseases with high prevalence in areas of endemicity would strongly benefit from availability of
postexposure vaccines. The development of these vaccines against mycobacterial infections, such as (para)tuberculosis, is hampered
by lack of experience in natural hosts. Paratuberculosis in cattle is both a mycobacterial disease of worldwide importance
and a natural host model for mycobacterial infections in general. The present study showed beneficial effects of therapeutic heat
shock protein 70 (Hsp70) vaccination in cattle with naturally acquired chronic infection with Mycobacterium avium subsp.
paratuberculosis. Vaccination-induced protection was associated with antibody responses, rather than with induction of specific
T helper 1 cells. Targeted therapeutic postexposure vaccination complementary to selective use of antibiotics could be an effective
approach for control of chronic mycobacterial infections.