Conjugation with an Inulin-Chitosan Adjuvant Markedly Improves the Immunogenicity of Mycobacterium tuberculosis CFP10-TB10.4 Fusion Protein
Conjugation with an Inulin-Chitosan Adjuvant Markedly Improves the Immunogenicity of Mycobacterium tuberculosis CFP10-TB10.4 Fusion Protein
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与菊粉-壳聚糖佐剂缀合可显着提高结核分枝杆菌 CFP10-TB10.4 融合蛋白的免疫原性。
DOI：
10.1021/acs.molpharmaceut.6b00138
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发表时间：
2016-11-01
影响因子：
4.9
通讯作者：
He, Tao
中科院分区：
文献类型：
--
作者：
Yu, Weili;He, Tao
基于蛋白质的疫苗是应对结核分枝杆菌（Mtb）所带来的严峻形势的潜力。由于Mtb蛋白抗原固有的免疫原性差，需要有效的免疫刺激佐剂来增强对Mtb蛋白抗原的细胞和体液免疫应答。菊粉和壳聚糖（Cs）是可用于实现该目的的多糖佐剂。菊粉-Cs缀合物（菊粉-Cs）通过菊粉和Cs的协同相互作用充当有效佐剂。CFP 10和TB10.4是结核分枝杆菌两种重要的毒力蛋白抗原。构建CFP 10-TB10.4融合蛋白（CT），并将其作为蛋白抗原。本研究通过将CT与菊粉-Cs共价结合，制备了一种佐剂传递系统（菊粉-Cs-CT）。与菊粉-Cs的缀合物显著增加了CT的流体动力学体积，并且不改变CT的结构。高水平的Th 1型细胞因子（IFN-γ、TNF-α和IL-2）和Th 2型细胞因子（IL-4）通过菊粉-Cs-CT的激发而分泌。菊糖Cs CT引起高CT特异性抗体滴度，主要以IgG 1和IgG 2b的形式。药代动力学表明，与菊糖-Cs结合可以延长CT对免疫系统的血清暴露。药效学表明，与菊粉-Cs的缀合导致CT特异性IgG的有效产生。因此，菊糖-Cs的缀合可用作有效的佐剂递送系统以改善Mtb蛋白抗原的免疫原性。
Protein-based vaccines are of potential to deal with the severe situations posed by Mycobacterium tuberculosis (Mtb). Due to inherently poor immunogenicity of Mtb protein antigens, a potent immunostimulatory adjuvant is needed to enhance the cellular and humoral immune response to Mtb protein antigens. Inulin and chitosan (Cs) are polysaccharide adjuvants that can be used to achieve such an objective. The inulin-Cs conjugate (inulin-Cs) acted as a potent adjuvant through a synergistic interaction of inulin and Cs. CFP10 and TB10.4 are two important virulent protein antigens of Mtb. The CFP10-TB10.4 fusion protein (CT) was constructed and used as the protein antigen. In the present study, an adjuvant delivery system (inulin-Cs-CT) was developed by covalent conjugation of CT with inulin-Cs. Conjugation with inulin-Cs significantly increased the hydrodynamic volume of CT and did not alter the structure of CT. High levels of Thl-type cytokines (IFN-gamma, TNF-alpha, and IL-2) and Th2-type cytokine (IL-4) were secreted by provocation of inulin-Cs-CT. Inulin Cs CT elicited high CT-specific antibody titers, mostly in the form of IgG1 and IgG2b. Pharmacokinetics revealed that conjugation with inulin-Cs could prolong the serum exposure of CT to the immune system. Pharmacodynamics suggested that conjugation with inulin-Cs led to an efficient production of CT-specific IgG. Thus, conjugation of inulin-Cs can serve as a potent adjuvant delivery system to improve the immunogenicity of the Mtb protein antigens.