Flores-Valdez Mario A, Pedroza-Roldán César, Aceves-Sánchez Michel de Jesús, Peterson Eliza J R, Baliga Nitin S, Hernández-Pando Rogelio, Troudt JoLynn, Creissen Elizabeth, Izzo Linda, Bielefeldt-Ohmann Helle, Bickett Thomas, Izzo Angelo A
Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Mexico.
Departamento de Medicina Veterinaria, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Zapopan, Mexico.
Front Microbiol. 2018 Jun 12;9:1281. doi: 10.3389/fmicb.2018.01281. eCollection 2018.
(), the causative agent of human tuberculosis (TB), is estimated to be harbored by up to 2 billion people in a latent TB infection (LTBI) state. The only TB vaccine approved for use in humans, BCG, does not confer protection against establishment of or reactivation from LTBI, so new vaccine candidates are needed to specifically address this need. Following the hypothesis that mycobacterial biofilms resemble aspects of LTBI, we modified BCG by deleting the gene to create the BCGΔBCG1419c vaccine strain. In this study, we compared cytokine profiles, bacterial burden, and lung lesions after immunization with BCG or BCGΔBCG1419c before and after 6 months of aerosol infection with H37Rv in the resistant C57BL/6 mouse model. Our results show that in infected mice, BCGΔBCG1419c significantly reduced lung lesions and IL-6 in comparison to the unmodified BCG strain, and was the only vaccine that decreased production of TNF-α and IL-10 compared to non-vaccinated mice, while vaccination with BCG or BCGΔBCG1419c significantly reduced IFN-γ production. Moreover, transcriptome profiling of BCGΔBCG1419c suggests that compared to BCG, it has decreased expression of genes involved in mycolic acids (MAs) metabolism, and antigenic chaperones, which might be involved in reduced pathology compared to BCG-vaccinated mice.
结核分枝杆菌（Mycobacterium tuberculosis）是人类结核病（TB）的病原体，据估计，多达20亿人处于潜伏性结核感染（LTBI）状态并携带该病菌。唯一被批准用于人类的结核病疫苗卡介苗（BCG）并不能预防LTBI的发生或再激活，因此需要新的候选疫苗来专门满足这一需求。基于分枝杆菌生物膜类似于LTBI某些方面的假说，我们通过删除BCG1419c基因对卡介苗进行改造，创建了BCGΔBCG1419c疫苗株。在本研究中，我们在抗性C57BL/6小鼠模型中，比较了用卡介苗或BCGΔBCG1419c免疫后，再经气溶胶感染H37Rv 6个月前后的细胞因子谱、细菌载量和肺部病变情况。我们的结果表明，在感染小鼠中，与未改造的卡介苗菌株相比，BCGΔBCG1419c显著减少了肺部病变和白细胞介素-6（IL-6），并且与未接种疫苗的小鼠相比，它是唯一能降低肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）产生的疫苗，而接种卡介苗或BCGΔBCG1419c均显著降低了干扰素-γ（IFN-γ）的产生。此外，BCGΔBCG1419c的转录组分析表明，与卡介苗相比，它参与分枝菌酸（MAs）代谢和抗原伴侣的基因表达降低，这可能与相较于接种卡介苗的小鼠病理变化减轻有关。
