Enhancement of immunocompetence in tuberculosis by DNA vaccination.

Our studies in mice show that DNA vaccines, initially designed to prevent infection, can have a dramatic therapeutic action too. In heavily infected mice, simply by giving DNA vaccination, the immune response can be caused to switch from one that is relatively inefficient and gives bacterial stasis to one that kills the bacteria, and persistent bacteria can be eliminated. Adoptive transfer of protection with T cell clones and in vitro tests of clone function indicate that the effects are probably mainly mediated by antigen specific CD8+/CD4-/CD44hi T cells that both produce gamma-interferon and kill the bacteria during granule-dependent lysis of infected macrophages. We can speculate that application of such immunotherapy in conjunction with conventional chemotherapeutic antibacterial drugs might result in faster or more certain cure of the disease in man. Furthermore, similar vaccines used prophylactically and therapeutically might be able to both prevent establishment of this persistent state and eliminate it if it is already established.