rBCG30-Induced Immunity and Cross-Protection against Mycobacterium leprae Challenge Are Enhanced by Boosting with the Mycobacterium tuberculosis 30-Kilodalton Antigen 85B

Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimalMycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG againstMycobacterium tu-berculosis andMycobacterium bovis challenge in animal models, for efficacy againstMycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses theM. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85 % homolo-gous with theM. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viableM. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating theM. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection againstM. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purifiedM. tuberculosis orM. leprae antigen 85B also induced protection againstM. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 withM. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly aug-mented protection againstM. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection againstM. tuberculo-sis, induces cross-protection againstM. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy