rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge is enhanced by boosting with Mycobacterium tuberculosis 30-kDa Antigen 85B.

Leprosy remains a major global health problem and typically occurs in regions endemic for tuberculosis. Vaccines are needed that protect against both infections, and do so better than the suboptimal BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein Antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham-immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind foot pad. After 7 months, vaccine efficacy was assessed by enumerating M. leprae/ foot pad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than BCG. Immunization of mice with purified M. tuberculosis or M. leprae Antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis Antigen 85B significantly enhanced r30ML-specific immune responses, and substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to BCG, and boosting rBCG30 with Antigen 85B further enhances immune responses and protective efficacy.