Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Biochemistry, Payam-e Noor University (PNU), P.O.Box: 91735-433, Mashhad, Iran.
Microb Pathog. 2019 Apr;129:68-73. doi: 10.1016/j.micpath.2019.01.045. Epub 2019 Jan 31.
Introducing an effective vaccine for tuberculosis (TB) is an urgent need. Mycobacterium tuberculosis (Mtb) Ag85 complex is suggested for making protective immunodominant antigens for design and development of novel TB vaccine. In the present study, a pDR2EF1-Fcγ1 vector has been used to make Ag85B:hFcγ1 recombinant fusion protein. Briefly, specific XbaI and NotI site incorporated primers were used to amplify Mtb-fbpB gene by PCR, TA-cloned and amplified in E.coli DH5α. The resulting vector then subcloned into the pDR2EF1.Fcγ1 vector and transferred to Chinese hamster ovary (CHO) cell line. DNA sequencing was performed to confirm that Ag85B:hFcγ1 construct is precise and in-frame. Then, Ag85B:hFcγ1 protein was produced by CHO expression system and recombinant protein was purified using HiTrap rProtein A Sepharose Fast Flow column. The presence of recombinant fusion protein confirmed by immunofluorescence (IFA) and Western blotting (WB). This fusion protein containing Fc fragment of human IgG1, apart from stability and adjuvanticity potential, could bind to FcRγI (CD64) on the surface of antigen-presenting cells (APCs) and induce cross-presentation in favour of host immune response and can be used as a potential candidate along with other subunit vaccines against Mtb.
引入一种有效的结核病(TB)疫苗是当务之急。结核分枝杆菌(Mtb)Ag85 复合物被建议用于设计和开发新型结核疫苗的保护性免疫显性抗原。在本研究中,使用了 pDR2EF1-Fcγ1 载体来构建 Ag85B:hFcγ1 重组融合蛋白。简要地说,使用带有特定 XbaI 和 NotI 位点的引物通过 PCR 扩增 Mtb-fbpB 基因,TA 克隆并在大肠杆菌 DH5α 中扩增。然后,将所得载体亚克隆到 pDR2EF1.Fcγ1 载体中,并转移到中国仓鼠卵巢(CHO)细胞系中。进行 DNA 测序以确认 Ag85B:hFcγ1 构建体是精确的和框内的。然后,通过 CHO 表达系统生产 Ag85B:hFcγ1 蛋白,并使用 HiTrap rProtein A Sepharose Fast Flow 柱纯化重组蛋白。通过免疫荧光(IFA)和 Western blot(WB)确认重组融合蛋白的存在。该融合蛋白含有人 IgG1 的 Fc 片段,除了具有稳定性和佐剂潜力外,还可以与抗原呈递细胞(APC)表面的 FcRγI(CD64)结合,有利于宿主免疫反应的交叉呈递,并可与其他亚单位疫苗一起用作针对 Mtb 的潜在候选物。