This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Tuberculosis (TB) remains a global health burden for which safe and novel vaccine strategies are needed. Live attenuated Mycobacterium tuberculosis mutants are of interest because of the limitations of BCG as a TB vaccine. Critical to the use of live attenuated Mycobacterium tuberculosis mutants is their documentation of safety in non-human primates. In this study, we describe studies that evaluate the safety and efficacy of two live attenuated M. tuberculosis double deletion vaccine strains (mc^2 6020 (lysA panCD) and mc^2 6030 (RD1 panCD) in the non-human primate model. mc^2 6020 is a rapidly cleared strain and mc^2 6030 is a persistent strain. To test safety, an intradermal injection of 9 x 10^6 CFU/mL (50-times the equivalent human dose of BCG) of mc^2 6020 or mc^2 6030 was administered. Both live attenuated M. tuberculosis vaccine strains were safe and well tolerated. Following a high dose intrabronchial challenge with virulent M. tuberculosis, BCG vaccinated animals had reduced pathology compared to mc^2 6020, mc^2 6030, and unvaccinated controls. Both non-replicating and limited replicating live attenuated M. tuberculosis vaccine candidates represent safe alternatives to BCG for TB vaccination.
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