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来自结核分枝杆菌的抗原自组装成颗粒疫苗的免疫原性。

Immunogencity of antigens from Mycobacterium tuberculosis self-assembled as particulate vaccines.

作者信息

Rubio Reyes Patricia, Parlane Natalie A, Wedlock D Neil, Rehm Bernd H A

机构信息

Institute of Fundamental Sciences, Massey University, Private Bag 11222, Palmerston North, New Zealand.

AgResearch, Hopkirk Research Institute, Palmerston North, New Zealand.

出版信息

Int J Med Microbiol. 2016 Dec;306(8):624-632. doi: 10.1016/j.ijmm.2016.10.002. Epub 2016 Oct 13.

Abstract

Traditional approaches to vaccine development have failed to identify better vaccines to replace or supplement BCG for the control of tuberculosis (TB). Subunit vaccines offer a safer and more reproducible alternative for the prevention of diseases. In this study, the immunogenicity of bacterially derived polyester beads displaying three different Rv antigens of Mycobacterium tuberculosis was evaluated. Polyester beads displaying the antigens Rv1626, Rv2032, Rv1789, respectively, were produced in an endotoxin-free Escherichia coli strain. Beads were formulated with the adjuvant DDA and subcutaneously administered to C57BL/6 mice. Cytokine responses were evaluated by CBA and antibody responses by ELISA. Specificity of the IgG response was assessed by immunoblotting cell lysates of the vaccine production strains using sera from the vaccinated mice. Mice vaccinated with beads displaying Rv1626 had significantly greater IgG1 responses compared to mice vaccinated with Rv1789 beads and greater IgG2 responses than the group vaccinated with Rv2032 beads (p<0.05). Immunoblotting of antisera from these mice indicated the antibody responses were Rv1626 antigen-specific and there was no detectable immune response to the polyester component of the vaccine. Overall, this study suggested that selected TB antigens derived from reverse vaccinology approaches can be displayed on polyester beads to produce antigen-specific immune responses potentially relevant to the prevention of TB.

摘要

传统的疫苗开发方法未能找到更好的疫苗来替代或补充卡介苗以控制结核病(TB)。亚单位疫苗为疾病预防提供了一种更安全且更具可重复性的选择。在本研究中,评估了展示结核分枝杆菌三种不同Rv抗原的细菌衍生聚酯珠的免疫原性。分别展示抗原Rv1626、Rv2032、Rv1789的聚酯珠在无内毒素的大肠杆菌菌株中生产。珠子与佐剂DDA配制后皮下注射给C57BL / 6小鼠。通过CBA评估细胞因子反应,通过ELISA评估抗体反应。使用接种小鼠的血清对疫苗生产菌株的细胞裂解物进行免疫印迹,以评估IgG反应的特异性。与接种Rv1789珠子的小鼠相比,接种展示Rv1626珠子的小鼠具有显著更高的IgG1反应,且比接种Rv2032珠子的组具有更高的IgG2反应(p<0.05)。这些小鼠抗血清的免疫印迹表明抗体反应是Rv1626抗原特异性的,并且对疫苗的聚酯成分没有可检测到的免疫反应。总体而言,本研究表明,源自反向疫苗学方法的选定结核抗原可以展示在聚酯珠上,以产生可能与结核病预防相关的抗原特异性免疫反应。

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