Expanding the antigenic repertoire of BCG improves protective efficacy against aerosol Mycobacterium tuberculosis infection.

We have developed a strain of the tuberculosis vaccine Mycobacterium bovis bacille Calmette Guerin (BCG) that secretes high levels of a fusion protein comprising the immunodominant Mycobacterium tuberculosis Ag85B and ESAT-6 (BCG85B-ES). Mice vaccinated with BCG85B-ES were significantly better protected in the lung against aerosol infection with virulent M. tuberculosis than animals immunized with control BCG. The growth characteristic of BCG85B-ES in host tissue was identical to control BCG, suggesting the improved protective efficacy was directly related to the expression of the Ag85B-ESAT-6 fusion protein. These results suggest that BCG85B-ES warrants further investigation to determine its suitability to control tuberculosis in humans.