Abstract
The incidence of infections with nontuberculous mycobacteria (NTM) has been increasing worldwide. The emergence of multidrug-resistant NTM is a serious clinical concern, and a vaccine for NTM has not yet been developed. We previously developed a new recombinant Bacillus Calmette–Guérin (rBCG) vaccine encoding the antigen 85B (Ag85B) protein of Mycobacterium kansasii—termed rBCG-Mkan85B—which was used together with a booster immunization with plasmid DNA expressing the same M. kansasii Ag85B gene (DNA-Mkan85B). We reported that rBCG-Mkan85B/DNA-Mkan85B prime–boost immunization elicited various NTM strain-specific CD4+ and CD8+ T cells and induced Mycobacterium tuberculosis-specific immunity. In this study, to investigate the protective effect against M. kansasii infection, we challenged mice vaccinated with a rBCG-Mkan85B or rBCG-Mkan85B/DNA-Mkan85B prime–boost strategy with virulent M. kansasii. Although BCG and rBCG-Mkan85B immunization each suppressed the growth of M. kansasii in the mouse lungs, the rBCG-Mkan85B/DNA-Mkan85B prime–boost vaccination reduced the bacterial burden more significantly. Moreover, the rBCG-Mkan85B/DNA-Mkan85B prime–boost vaccination induced antigen-specific CD4+ and CD8+ T cells. Our data suggest that rBCG-Mkan85B/DNA-Mkan85B prime–boost vaccination effectively enhances antigen-specific T cells. Our novel rBCG could be a potential alternative to clinical BCG for preventing various NTM infections.
Highlights
Nontuberculous mycobacteria (NTM) are mycobacterium species other than the Mycobacterium tuberculosis complex and Mycobacterium leprae, such as Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium kansasii
Bacillus Calmette–Guérin (BCG) or recombinant Bacillus Calmette–Guérin (rBCG)-Mkan85B Vaccination Protects against M. kansasii Infection
According to previous epidemiological reports, BCG vaccination can reduce the risk of NTM infection in humans [19,20,21]
Summary
Nontuberculous mycobacteria (NTM) are mycobacterium species other than the Mycobacterium tuberculosis complex and Mycobacterium leprae, such as Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium kansasii. The incidence of NTM infection has been increasing worldwide [1,2,3]. Since NTM pathogens are intracellular, cell-mediated immunity plays a major role in protecting against NTM. Previous reports have indicated that protective immunity against tuberculosis (TB) and NTM infection might overlap [9]. Epidemiological data suggest that latent TB infection decreases the risk of NTM diseases [9], and a systematic review found that an increased proportion of NTM diseases were related to coincidental decreases in TB [10]. Several reports have indicated that Bacillus Calmette–Guérin (BCG)—
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