Tuberculosis continues to ravage humanity, killing 2 million people yearly. Most cases occur in areas of the world to which the disease is endemic, where almost everyone is vaccinated early in life with Mycobacterium bovis BCG, the currently available
vaccine against
tuberculosis. Thus, while more-potent
vaccines are needed to replace BCG, new
vaccines are also needed to boost the immune protection of the 4 billion people already vaccinated with BCG. Until now, no booster
vaccine has been shown capable of significantly enhancing the level of protective immunity induced by BCG in the stringent guinea pig model of
pulmonary tuberculosis, the "gold standard" for testing
tuberculosis vaccines. In this paper, we describe a booster
vaccine for BCG comprising the purified recombinant Mycobacterium tuberculosis 30-kDa
protein, the major secreted
protein of this pathogen. In the guinea pig model of
pulmonary tuberculosis, boosting BCG-immunized animals once with the 30-kDa
protein greatly increased cell-mediated and humoral immune responses to the
protein in three consecutive experiments. Most importantly, boosting BCG-immunized animals once with the 30-kDa
protein significantly enhanced protective immunity against
aerosol challenge with highly virulent M.
tuberculosis, as evidenced by a significantly reduced lung and spleen burden of M.
tuberculosis compared with those for nonboosted BCG-immunized animals (mean additional reduction in CFU of 0.4 +/- 0.1 log in the lung [P = 0.03] and 0.6 +/- 0.1 log in the spleen [P = 0.002]). This study suggests that administering BCG-immunized people a booster
vaccine comprising the 30-kDa
protein may enhance their level of immunoprotection against
tuberculosis.