Mycobacterium tuberculosis continues to kill about 3 million people every y
ear(1), more than any other single infectious agent, This is attributed pri
marily to an inadequate immune response towards infecting bacteria, which s
uffer growth inhibition rather than death and subsequently multiply catastr
ophically. Although the bacillus Calmette-Guerin (BCG) vaccine is widely us
ed, it has major limitations as a preventative measure(2), In addition, eff
ective treatment requires that patients take large doses of antibacterial d
rug combinations for at least 6 months after diagnosis(3), which is difficu
lt to achieve in many parts of the world and is further restricted by the e
mergence of multidrug-resistant strains of M. tuberculosis, In these circum
stances, immunotherapy to boost the efficiency of the immune system in infe
cted patients could be a valuable adjunct to antibacterial chemotherapy(4),
Here we show in mice that DNA vaccines, initially designed to prevent infe
ction, can also have a pronounced therapeutic action, In heavily infected m
ice, DNA vaccinations can switch the immune response from one that is relat
ively inefficient and gives bacterial stasis to one that kills bacteria, Ap
plication of such immunotherapy in conjunction with conventional chemothera
peutic antibacterial drugs might result in faster or more certain cure of t
he disease in humans.