Tuberculosis remains a serious global health problem. BCG is the only prophylactic TB vaccine and it shows variable protective efficacy. Chimeric protein subunit vaccines hold great potential as stand-alone vaccines or heterologous BCG prime boosters. We have designed a protein chimera, PP31, by combining Mtb ESAT-6 family antigen Rv1198 and MoCo biosynthesis family antigen Rv3111. Further, PP31 was extended by addition of latency antigen Rv1813c to yield PP43. Immunization of BALB/c mice with PP31 or PP43 with FIA adjuvant elicited strong humoral immune response. Restimulation of splenocytes of the immunized mice lead to significant proliferation of lymphocytes, secretion of cytokines IFN-γ, TNF, IL-2 of the Th1 class, IL-17A of the Th17 class, and IL-6. PP31 and PP43 also induced intracellular cytokine expression (IFN-γ, TNF, and IL-2) from both CD4⁺-CD44^high and CD8⁺-CD44^high T-cells. Antigen-specific IFN-γ⁺/IL-2⁺ double positive CD4⁺ T-cells were significantly higher in case of PP43 than PP31-immunized mice and control group. PP43 showed protection equivalent to heat-inactivated BCG in response to challenge of the immunized mice with Mtb H37Ra. Based on its immunogenicity and protective efficacy, PP43 appears to be a potential candidate for further development as a subunit vaccine against TB.

结核病仍然是一个严重的全球健康问题。BCG 是唯一的预防性结核病疫苗，它显示出不同的保护功效。嵌合蛋白亚单位疫苗作为独立疫苗或异源 BCG 增强剂具有巨大潜力。我们设计了一种蛋白质嵌合体，PP31，通过结合MtbESAT-6 家族抗原 Rv1198 和 MoCo 生物合成家族抗原 Rv3111。此外，通过添加潜伏抗原 Rv1813c 来扩展 PP31 以产生 PP43。用带有 FIA 佐剂的 PP31 或 PP43 对 BALB/c 小鼠进行免疫接种引发了强烈的体液免疫反应。免疫小鼠脾细胞的再刺激导致淋巴细胞显着增殖，分泌细胞因子 IFN-γ、TNF、Th1 类的 IL-2、Th17 类的 IL-17A 和 IL-6。PP31 和 PP43 还诱导来自 CD4 ⁺ -CD44^高和 CD8 ⁺ -CD44^高T 细胞的细胞内细胞因子表达（IFN-γ、TNF 和 IL-2）。抗原特异性 IFN-γ ⁺ /IL-2 ⁺双阳性 CD4 ⁺PP43 的 T 细胞明显高于 PP31 免疫的小鼠和对照组。PP43 显示出相当于热灭活 BCG 的保护作用，以响应Mtb H37Ra对免疫小鼠的攻击。基于其免疫原性和保护功效，PP43 似乎是进一步开发作为抗结核亚单位疫苗的潜在候选物。