ABSTRACTLeprosy 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 bovisBCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG againstMycobacterium tuberculosisandMycobacterium bovischallenge in animal models, for efficacy againstMycobacterium lepraechallenge in a murine model of leprosy. rBCG30 overexpresses theM. tuberculosis30-kDa major secretory protein antigen 85B, which is 85% homologous with theM. lepraehomolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viableM. lepraeinto each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating theM. lepraebacteria per footpad. Both BCG and rBCG30 induced significant protection againstM. lepraechallenge. 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. tuberculosisorM. lepraeantigen 85B also induced protection againstM. lepraechallenge but less so than BCG or rBCG30. Notably, boosting rBCG30 withM. tuberculosisantigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection againstM. lepraechallenge. Thus, rBCG30, a vaccine that induces improved protection againstM. tuberculosis, induces cross-protection againstM. lepraethat is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy.
A Comprehensive Map of Mycobacterium tuberculosis Complex Regions of Difference