National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
Department of Biochemistry, Jamia Hamdard, New Delhi, 110062, India.
Sci Rep. 2021 Feb 4;11(1):3049. doi: 10.1038/s41598-021-82614-5.
Due to the limited utility of Bacillus Calmette-Guérin (BCG), the only approved vaccine available for tuberculosis, there is a need to develop a more effective and safe vaccine. We evaluated the safety and efficacy of a dry powder aerosol (DPA) formulation of BCG encapsulated alginate particle (BEAP) and the conventional intradermal BCG immunization in infant rhesus macaques (Macaca mulatta). The infant macaques were immunized intratracheally with DPA of BEAP into the lungs. Animals were monitored for their growth, behaviour, any adverse and allergic response. The protective efficacy of BEAP was estimated by the ex-vivo H37Rv infection method. Post-immunization with BEAP, granulocytes count, weight gain, chest radiography, levels of liver secreted enzymes, cytokines associated with inflammation like TNF and IL-6 established that BEAP is non-toxic and it does not elicit an allergic response. The T cells isolated from BEAP immunized animals' blood, upon stimulation with M.tb antigen, secreted high levels of IFN-γ, TNF, IL-6 and IL-2. The activated T cells from BEAP group, when co-cultured with M.tb infected macrophages, eliminated largest number of infected macrophages compared to the BCG and control group. This study suggests the safety and efficacy of BEAP in Non-human primate model.
由于卡介苗（BCG）的应用有限，而 BCG 是唯一获准用于结核病的疫苗，因此需要开发更有效和安全的疫苗。我们评估了海藻酸钠颗粒包被的冻干粉气溶胶（DPA）制剂（BEAP）和常规皮内 BCG 免疫在婴儿恒河猴（Macaca mulatta）中的安全性和有效性。婴儿恒河猴通过气管内吸入将 DPA 递送至肺部。对动物的生长、行为、任何不良反应和过敏反应进行监测。通过体外 H37Rv 感染方法估计 BEAP 的保护效力。接种 BEAP 后，通过对嗜中性粒细胞计数、体重增加、胸部 X 光检查、肝脏分泌酶的水平、与 TNF 和 IL-6 等炎症相关的细胞因子进行检测，发现 BEAP 是无毒的，不会引起过敏反应。从 BEAP 免疫动物的血液中分离出的 T 细胞，在受到 M.tb 抗原刺激后，分泌高水平的 IFN-γ、TNF、IL-6 和 IL-2。与 BCG 和对照组相比，来自 BEAP 组的激活的 T 细胞在与感染了 M.tb 的巨噬细胞共培养时，能够清除最多数量的感染巨噬细胞。这项研究表明，BEAP 在非人类灵长类动物模型中是安全有效的。
