The dream of a vaccine against tuberculosis; new vaccines improving or replacing BCG?

In the last 10 yrs, work with experimental laboratory models has developed many new vaccine candidates against tuberculosis (TB). They include subunit vaccines, modified bacilli Calmette-Guérin (BCG) and attenuated Mycobacterium tuberculosis. Phase I clinical trials of new TB vaccine candidates have begun for the first time after 80 yrs of use of BCG. Many of these new trials involve recombinant BCG or improve BCG immunity by boosting with vaccines consisting of subunits or attenuated vaccinia virus expressing TB antigens. However, effective vaccination against TB presents diverse and complex challenges. For example, TB infection can become reactivated years later and infection does not guarantee resistance to a subsequent second infection. A truly effective TB vaccine may, therefore, have to elicit an immune response that is greater than that induced by natural infection. In addition, various different populations have to be protected including those vaccinated with BCG and those infected with M. tuberculosis or HIV. The goal is a new generation of vaccines effective against respiratory forms of tuberculosis. As a first step, good candidate vaccines able to boost bacille Calmette-Guérin and thereby improve protection could be a reality in the near future. Tuberculosis vaccine candidates, able to replace the currently used bacille Calmette-Guérin and/or make the eradication of tuberculosis feasible, can only be expected in the long-term, and safe live vaccines could be promising candidates.