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结核分枝杆菌新型抗原与 MPLA 佐剂共包封于 PLGA:DDA 杂化纳米粒中,可刺激黏膜和系统免疫。

A novel antigen of Mycobacterium tuberculosis and MPLA adjuvant co-entrapped into PLGA:DDA hybrid nanoparticles stimulates mucosal and systemic immunity.

机构信息

Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.

Department of Medical Bacteriology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Microb Pathog. 2018 Dec;125:507-513. doi: 10.1016/j.micpath.2018.10.023. Epub 2018 Oct 21.

Abstract

BACKGROUND

Due to initiation of Mycobacterium tuberculosis infection via the mucosal tissue of the respiratory tract, intranasal administration of new tuberculosis vaccines is highly regarded to enhance mucosal immunity. Our outline was evaluation of mucosal and systemic immune responses in BALB/c mice after nasal delivery of HspX/EsxS fused antigen of Mycobacterium tuberculosis along with MPLA adjuvant entrapped in PLGA:DDA hybrid nanoparticles.

METHODS

In this study, the double emulsion solvent evaporation method (w/o/w) was used to prepare different nanoparticle formulations containing HspX/EsxS protein and MPLA. Three weeks after the last nasal immunization of BALB/c mice, IgA antibody levels in nasal lavage and IFN-γ, IL-4, IL-17 and TGF-β cytokines in supernatant of cultured splenocytes and also serum IgG1 and IgG2a titers were evaluated using ELISA method.

RESULTS

Our results indicated that nasal vaccination with PLGA:DDA nanoparticles loaded with HspX/EsxS protein±MPLA, both with and without a prime dose of BCG could provide efficient Th1, Th17, IgA, IgG1 and IgG2a immune responses.

CONCLUSION

These findings demonstrate that both PLGA:DDA hybrid nanoparticles as carrier/adjuvant and MPLA as adjuvant, could efficiently induce mucosal and systemic immune responses against HspX/EsxS antigen, alone or as a booster for BCG.

摘要

背景

由于结核分枝杆菌感染是通过呼吸道的黏膜组织引发的,因此鼻腔内给予新的结核病疫苗被认为可以增强黏膜免疫。我们的方案是评估经鼻给予结核分枝杆菌 HspX/EsxS 融合抗原和 MPLA 佐剂包封于 PLGA:DDA 杂化纳米颗粒后 BALB/c 小鼠的黏膜和系统免疫应答。

方法

在这项研究中,使用双乳液溶剂蒸发法(w/o/w)制备了含有 HspX/EsxS 蛋白和 MPLA 的不同纳米颗粒制剂。在 BALB/c 小鼠最后一次鼻内免疫 3 周后,通过 ELISA 法评估鼻洗液中的 IgA 抗体水平以及培养的脾细胞上清液中的 IFN-γ、IL-4、IL-17 和 TGF-β细胞因子,以及血清 IgG1 和 IgG2a 滴度。

结果

我们的结果表明,用 PLGA:DDA 纳米颗粒负载 HspX/EsxS 蛋白±MPLA 进行鼻内免疫,无论是与 BCG 进行初免还是加强免疫,都能提供有效的 Th1、Th17、IgA、IgG1 和 IgG2a 免疫应答。

结论

这些发现表明,PLGA:DDA 杂化纳米颗粒作为载体/佐剂以及 MPLA 作为佐剂,均能单独或作为 BCG 的加强剂,有效诱导针对 HspX/EsxS 抗原的黏膜和系统免疫应答。

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