Progress towards a new tuberculosis vaccine.

New weapons are needed in the fight against tuberculosis, both antibacterial drugs and a vaccine. If one new antituberculosis drug is developed it will encounter emerging resistance; at least two are needed, to be used in combination only. This is a complicated and difficult goal. In contrast, an effective new vaccine would have multiple antigenic targets within the bacterium, making the emergence of resistance to the vaccine unlikely. This is a simpler goal to achieve, and recent research indicates that it 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; the vaccine must target antigens produced by actively multiplying bacteria as well as growth-inhibited bacteria. Consistent with this, the protective antigens have been found among secreted and stress proteins (for example Ag85, ESAT-6, hsp65, hsp70). Species-specific antigens are not required, so 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 superior to recombinant mycobacterial or viral vectors for this purpose.