Product Development Cell 1, National Institute of Immunology, J.N.U Complex, Aruna Asaf Ali Marg, New Delhi 110067, India.
Vaccine. 2012 Sep 21;30(43):6198-209. doi: 10.1016/j.vaccine.2012.07.061. Epub 2012 Aug 4.
Tuberculosis kills two million people each year. As the current vaccine BCG fails to prevent adult cases of TB, an improved vaccine and/or vaccination strategy is urgently needed to combat TB. Previously we reported the higher protective efficacy of Mycobacterium indicus pranii (MIP), formerly known as Mycobacterium w (M.w) as compared to BCG in murine model of TB. In this study we further evaluated the protective efficacy of MIP in guinea pig model of TB. Modulation of post infection immune response was analyzed in the lungs of MIP immunized and control groups. We found reduced bacterial loads, improved pathology and organized granulomatous response at different post infection time points in the MIP-immunized group as compared to the BCG-immunized group. Combined results suggest that MIP-immunization results in heightened protective Th1 response as compared to BCG group, early after infection with M.tb and a balanced Th1 versus immunosuppressive response at late chronic stage of infection. The study demonstrates the higher antigen presenting cells function both inside the granuloma as well as in the single cell suspension of the lung in the MIP-immunized group. We further demonstrate that live MIP is safe to use in vivo as we observed quick clearance of MIP from the body and no untoward reaction was found. Aerosol route of immunization provided higher protection. Further this study provides evidence that MIP-immunization gives significantly better long term protection as compared to BCG against TB.
每年有 200 万人死于结核病。由于目前的卡介苗(BCG)疫苗不能预防成年人结核病,因此迫切需要一种改进的疫苗和/或接种策略来对抗结核病。此前我们报道了分枝杆菌印度变种(MIP),以前称为分枝杆菌 w(M.w)在预防结核病的小鼠模型中比 BCG 具有更高的保护效力。在这项研究中,我们进一步评估了 MIP 在豚鼠结核病模型中的保护效力。分析了 MIP 免疫组和对照组肺部感染后免疫反应的变化。与 BCG 免疫组相比,我们发现在不同的感染后时间点,MIP 免疫组的细菌载量降低,病理改善,并且有组织的肉芽肿反应。综合结果表明,与 BCG 组相比,MIP 免疫接种可诱导更高的保护性 Th1 反应,即在感染 M.tb 后早期,以及在感染的慢性晚期出现 Th1 与免疫抑制反应的平衡。该研究表明,MIP 免疫接种可增强抗原呈递细胞的功能,无论是在肉芽肿内还是在肺的单细胞悬浮液中。我们进一步证明,活 MIP 在体内使用是安全的,因为我们观察到 MIP 从体内迅速清除,并且没有发现不良反应。免疫接种的气溶胶途径提供了更高的保护。此外,这项研究提供了证据表明,与 BCG 相比,MIP 免疫接种可显著提高对结核病的长期保护作用。