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首页> 外文期刊>Vaccine >Pulmonary delivery of DNA encoding Mycobacterium tuberculosis latency antigen Rv1733c associated to PLGA-PEI nanoparticles enhances T cell responses in a DNA prime/protein boost vaccination regimen in mice.
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Pulmonary delivery of DNA encoding Mycobacterium tuberculosis latency antigen Rv1733c associated to PLGA-PEI nanoparticles enhances T cell responses in a DNA prime/protein boost vaccination regimen in mice.

机译:与PLGA-PEI纳米粒子相关的编码结核分枝杆菌潜伏期抗原Rv1733c的DNA的肺部递送增强了小鼠DNA初免/蛋白质加强免疫接种方案中的T细胞反应。

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During persistent infection and hypoxic-stress, Mycobacterium tuberculosis (Mtb) expresses a series of Mtb latency antigens. The aim of this study was to evaluate the immunogenicity of a DNA vaccine encoding the Mtb latency antigen Rv1733c and to explore the effect of pulmonary delivery and co-formulation with poly (D,L-lactide-co-glycolide) (PLGA)-polyethyleneimine (PEI) nanoparticles (np) on host immunity. Characterization studies indicated that PLGA-PEI np kept their nanometer size after concentration and were positively charged. The np were able to mature human dendritic cells and stimulated them to secrete IL-12 and TNF- alpha comparable to levels observed after lipopolysaccharide (LPS) stimulation. Mtb latency antigen Rv1733c DNA prime combined with Rv1733c protein boost enhanced T cell proliferation and IFN- gamma secretion in mice in response to Rv1733c and Mtb hypoxic lysate. Rv1733c DNA adsorbed to PLGA-PEI np and applied to the lungs increased T cell proliferation and IFN- gamma production more potently compared to the same vaccinations given intramuscularly. The strongest immunogenicity was obtained by pulmonary priming with np-adsorbed Rv1733c DNA followed by boosting with Rv1733c protein. These results confirm that PLGA-PEI np are an efficient DNA vaccine delivery system to enhance T cell responses through pulmonary delivery in a DNA prime/protein boost vaccine regimen.
机译:在持续感染和低氧应激期间,结核分枝杆菌( Mtb )表达一系列 Mtb 潜伏期抗原。这项研究的目的是评估编码 Mtb 潜伏期抗原Rv1733c的DNA疫苗的免疫原性,并探讨肺部递送和与聚(D,L-丙交酯-乙交酯(PLGA)-聚乙烯亚胺(PEI)纳米颗粒(np)对宿主的免疫力。表征研究表明,PLGA-PEI np浓缩后保持其纳米尺寸,并带正电。 np能够使人树突细胞成熟并刺激它们分泌与脂多糖(LPS)刺激后观察到的水平相当的IL-12和TNF-α。 Mtb潜伏期抗原Rv1733c DNA初免与Rv1733c蛋白结合可增强小鼠对Tv1733c和 Mtb 低氧裂解液的T细胞增殖和IFN-γ分泌。与肌肉内注射相同的疫苗相比,Rv1733c DNA吸附到PLGA-PEI np并应用于肺部后,可更有效地提高T细胞增殖和IFN-γ的产生。通过用np吸附的Rv1733c DNA进行肺启动,然后用Rv1733c蛋白加强免疫力,可获得最强的免疫原性。这些结果证实PLGA-PEI np是一种有效的DNA疫苗递送系统,可通过DNA初免/蛋白质加强疫苗方案中的肺部递送来增强T细胞反应。

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