Recombinant bacillus Calmette-Guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model

Tuberculosis (TB) continues to ravage humanity, causing 2 million deaths pe r year. A vaccine against Tn more potent than the current live vaccine, bac illus Calmette-Guerin (BCG). is desperately needed. Using two commercially available strains of BCC as host strains, BCC Connaught and Tice, we have c onstructed two recombinant BCC vaccines stably expressing and secreting the 30-kDa major secretory protein of Mycobacterium tuberculosis (M. tb.), the primary causative agent of Tn. We have tested the efficacy of the two stra ins in the highly susceptible guinea pig model of pulmonary TB, a model not eworthy for its close resemblance to human TB. Animals immunized with the r ecombinant BCG vaccines and challenged by aerosol with a highly Virulent st rain of M. tb. had 0.5 logs fewer M. tb. bacilli in their lungs and 1 log f ewer bacilli in their spleens on average than animals immunized with their parental conventional BCG Vaccine counterparts. Statistically, these differ ences were highly significant. Paralleling these results, at necropsy, anim als immunized with the recombinant BCG vaccines had fewer and smaller lesio ns in the lung, spleen, and liver and significantly less lung pathology tha n animals immunized with the parental BCC vaccines. The recombinant Vaccine s are the first Vaccines against TB more potent than the current commercial ly available BCC vaccines, which were developed nearly a century ago.