Tuberculosis (TB) remains a major and global problem of public health. An effective TB subunit vaccine is urgently needed. Proper selection of the delivery system for the vaccine is crucial for inducing an appropriate immune response tailored to control the target pathogen. In this study, we compared the immunogenicity and protective efficacy of CMFO subunit vaccines against primary progressive TB in two different adjuvant systems: the MTO oil-in-water (O/W) emulsion composed of monophosphoryl lipid A (MPL), trehalose-6,60-dibehenate (TDB), and oil in water emulsion MF59 and the DMT liposome containing dimethyldioctadecylammonium bromide (DDA), monophosphoryl lipid A (MPL), and trehalose-6,60-dibehenate (TDB). Our results demonstrated that the DMT-adjuvanted CMFO could confer more significant protection against M. tuberculosis infection than the CMFO/MTO did in mice. In particular, the adjuvant DMT showed a stronger ability than the O/W emulsion to adjuvant CMFO subunit vaccine and enhanced protection, attributed to elicit Th1-biased responses, strong Th1/Th17 cytokine responses, and IFN-γ⁺ or IL-2⁺ T cell responses. Therefore, our findings demonstrate that the liposome delivery system shows more effectiveness to adjuvant TB subunit vaccine than O/W emulsion and highlight the importance of adjuvant formulation for the better efficacy of a protein vaccine.

中文翻译：

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MTO和DMT佐剂的CMFO亚基疫苗针对结核分枝杆菌感染所产生的差异性免疫原性和保护功效。

结核病（TB）仍然是公共卫生的主要和全球性问题。迫切需要有效的结核亚单位疫苗。疫苗输送系统的正确选择对于诱导为控制目标病原体而设计的适当免疫反应至关重要。在这项研究中，我们比较了CMFO亚单位疫苗在两种不同的佐剂系统中对原发性进行性TB的免疫原性和保护效力：由单磷酰脂质A（MPL）组成的MTO水包油（O / W）乳液，海藻糖6 1,60-二苯二酸酯（TDB）和水包油乳剂MF59和DMT脂质体，其中含有二甲基二十八烷基溴化铵（DDA），单磷酰脂质A（MPL）和海藻糖-6,60-二苯甲酸酯（TDB）。我们的结果表明，DMT辅助的CMFO可以针对结核分枝杆菌感染比CMFO / MTO对小鼠的感染更大。特别是，佐剂DMT显示出比O / W乳剂更强的佐剂CMFO亚单位疫苗能力，并增强了保护作用，这归因于引发Th1偏向反应，强烈的Th1 / Th17细胞因子反应以及IFN- γ ⁺或IL-2 ⁺ T细胞反应。因此，我们的研究结果表明，脂质体递送系统对佐剂TB亚单位疫苗的疗效优于O / W乳剂，并突显了佐剂配方对于蛋白质疫苗更好疗效的重要性。