SUMMARY
Leprosy is best understood as two conjoined diseases. The first is a
chronic mycobacterial infection that elicits an extraordinary range of
cellular immune responses in humans. The second is a peripheral
neuropathy that is initiated by the infection and the accompanying
immunological events. The infection is curable but not preventable, and
leprosy remains a major global health problem, especially in the
developing world, publicity to the contrary notwithstanding.
Mycobacterium leprae remains noncultivable, and for over a
century leprosy has presented major challenges in the fields of
microbiology, pathology, immunology, and genetics; it continues to do
so today. This review focuses on recent advances in our understanding
of M. leprae and the host response to it, especially
concerning molecular identification of M. leprae, knowledge of
its genome, transcriptome, and proteome, its mechanisms of microbial
resistance, and recognition of strains by variable-number tandem repeat
analysis. Advances in experimental models include studies in gene
knockout mice and the development of molecular techniques to explore
the armadillo model. In clinical studies, notable progress has been
made concerning the immunology and immunopathology of leprosy, the
genetics of human resistance, mechanisms of nerve injury, and
chemotherapy. In nearly all of these areas, however, leprosy remains
poorly understood compared to other major bacterial
diseases.
Tuberculosis (TB) and leprosy still represent significant public health challenges, especially in low- and lower middle-income countries. Both poverty-related mycobacterial diseases require better tools to improve disease control. For leprosy, there has been an increased emphasis on developing tools for improved detection of infection and early diagnosis of disease. For TB, there has been a similar emphasis on such diagnostic tests, while increased research efforts have also focused on the development of new vaccines. Bacille Calmette–Guérin (BCG), the only available TB vaccine, provides insufficient and inconsistent protection to pulmonary TB in adults. The impact of BCG on leprosy, however, is significant, and the introduction of new TB vaccines that might replace BCG could, therefore, have serious impact also on leprosy. Given the similarities in antigenic makeup between the pathogens Mycobacterium tuberculosis (Mtb) and M. leprae, it is well possible, however, that new TB vaccines could cross-protect against leprosy. New TB subunit vaccines currently evaluated in human phase I and II studies indeed often contain antigens with homologs in M. leprae. In this review, we discuss pre-clinical studies and clinical trials of subunit or whole mycobacterial vaccines for TB and leprosy and reflect on the development of vaccines that could provide protection against both diseases. Furthermore, we provide the first preclinical evidence of such cross-protection by Mtb antigen 85B (Ag85B)-early secretory antigenic target (ESAT6) fusion recombinant proteins in in vivo mouse models of Mtb and M. leprae infection. We propose that preclinical integration and harmonization of TB and leprosy research should be considered and included in global strategies with respect to cross-protective vaccine research and development.
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