Komine-Aizawa Shihoko, Mizuno Satoru, Matsuo Kazuhiro, Namiki Takahiro, Hayakawa Satoshi, Honda Mitsuo
Department of Pathology and Microbiology, Division of Microbiology, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Japan BCG Laboratory, Tokyo 204-0022, Japan.
Vaccines (Basel). 2021 Nov 1;9(11):1260. doi: 10.3390/vaccines9111260.
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 -termed rBCG-Mkan85B-which was used together with a booster immunization with plasmid DNA expressing the same 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 -specific immunity. In this study, to investigate the protective effect against infection, we challenged mice vaccinated with a rBCG-Mkan85B or rBCG-Mkan85B/DNA-Mkan85B prime-boost strategy with virulent . Although BCG and rBCG-Mkan85B immunization each suppressed the growth of 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.
非结核分枝杆菌(NTM)感染的发生率在全球范围内一直在上升。多重耐药NTM的出现是一个严重的临床问题,并且尚未开发出针对NTM的疫苗。我们之前开发了一种新的重组卡介苗(rBCG)疫苗,其编码抗原85B(Ag85B)蛋白,命名为rBCG-Mkan85B,它与表达相同Ag85B基因的质粒DNA(DNA-Mkan85B)加强免疫联合使用。我们报道rBCG-Mkan85B/DNA-Mkan85B初免-加强免疫引发了各种NTM菌株特异性的CD4和CD8 T细胞,并诱导了特异性免疫。在本研究中,为了调查针对感染的保护作用,我们用强毒株对采用rBCG-Mkan85B或rBCG-Mkan85B/DNA-Mkan85B初免-加强策略接种疫苗的小鼠进行了攻击。尽管卡介苗和rBCG-Mkan85B免疫各自都抑制了小鼠肺部的生长,但rBCG-Mkan85B/DNA-Mkan85B初免-加强疫苗接种更显著地降低了细菌载量。此外,rBCG-Mkan85B/DNA-Mkan85B初免-加强疫苗接种诱导了抗原特异性的CD4和CD8 T细胞。我们的数据表明,rBCG-Mkan85B/DNA-Mkan85B初免-加强疫苗接种有效地增强了抗原特异性T细胞。我们的新型rBCG可能是临床卡介苗预防各种NTM感染的潜在替代品。