Genetic vaccination against tuberculosis.

New weapons are needed in the fight against tuberculosis. Recent research indicates that a vaccine better than BCG may be within reach. A diverse range of protein antigens can give encouragingly high levels of protective immunity in animal models when administered with adjuvants or as DNA vaccines. Accelerated arrest of bacterial multiplication followed by sustained decline in bacterial numbers are key parameters of protection and so the vaccine must target antigens produced by both actively multiplying and growth-inhibited bacteria. Consistent with this, the protective antigens have been found among secreted and stress proteins (e.g. Ag85, ESAT-6, hsp65, hsp70). Species-specific antigens are not needed, hence these remain available for diagnostic tests. Adoptive transfer of protection from vaccinated or infected mice into naive mice by transfer of purified T cells and clones shows that protection is expressed by antigen-specific cytotoxic T cells that produce interferon-gamma and lyse infected macrophages. These cells are produced in response to endogenous antigen. DNA vaccination appears to be an excellent way of generating these cells and may be able to give long-lasting protection.