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Multicomponent antituberculous subunit vaccine based on immunodominant antigens of Mycobacterium tuberculosis

机译:基于结核分枝杆菌免疫优势抗原的多组分抗结核亚单位疫苗

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摘要

The low molecular mass polypeptides of secretory proteome of Mycobacterium tuberculosis are dominant targets for recognition by lymphocytes of human models of immunity to tuberculosis. In the present study, we evaluated the inherent immunogenicity of 102 individual polypeptides purified from low molecular mass region below 40kDa in mouse model of immunization. The aim of this study was to identify molecules relevant for development of subunit vaccine against tuberculosis based on high degree of immunogenecity. Here, we demonstrate that experimental multicomponent subunit vaccine (MSV) consisting of five immunodominant polypeptides with high immunogenicity (CFP-25, CFP-20.5, Ag85B, Ag85A and CPF-32) induced both cellular and humoral immune responses characterized by Th1 and Th2 cytokine induction and imparted significant protection when administered with DDA-MPL adjuvants in C57BL/6J mice. The degree of protection imparted by experimental MSV on the basis of decrease in CFU's from target organs (lungs and spleen) was comparable to BCG and total mycobacterial culture filtrate proteins (CFPs) based vaccines. These results, therefore, suggest the potential of multicomponent subunit vaccination against tuberculosis based on strongly immunogenic proteins of M. tuberculosis.
机译:结核分枝杆菌分泌蛋白组的低分子量多肽是人类对结核病免疫模型的淋巴细胞识别的主要靶标。在本研究中,我们评估了在免疫小鼠模型中从40kDa以下的低分子量区域纯化的102个个体多肽的固有免疫原性。这项研究的目的是基于高度的免疫原性,鉴定与开发抗结核亚单位疫苗相关的分子。在这里,我们证明了由具有高免疫原性的五个免疫优势多肽(CFP-25,CFP-20.5,Ag85B,Ag85A和CPF-32)组成的实验性多组分亚单位疫苗(MSV)诱导了以Th1和Th2细胞因子为特征的细胞和体液免疫应答在C57BL / 6J小鼠中与DDA-MPL佐剂一起给药时,具有明显的诱导作用并具有显着保护作用。基于目标器官(肺和脾脏)CFU降低,实验性MSV赋予的保护程度可与BCG和基于总分枝杆菌培养物滤液蛋白(CFP)的疫苗相媲美。因此,这些结果表明,基于结核分枝杆菌的强免疫原性蛋白,针对肺结核的多组分亚单位疫苗的潜力。

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