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载有衣原体重组 MOMP 的 PLGA85:15 纳米粒的纳米疫苗制剂可增强免疫小鼠的 CD4 效应(CD44 CD62L)和记忆(CD44 CD62L)T 细胞。

A nanovaccine formulation of Chlamydia recombinant MOMP encapsulated in PLGA 85:15 nanoparticles augments CD4 effector (CD44 CD62L) and memory (CD44 CD62L) T-cells in immunized mice.

机构信息

Center for NanoBiotechnology & Life Sciences Research, Department of Biological Sciences, Alabama State University, Montgomery, AL, USA.

Instituto de Inmunología, Genética y Metabolismo (INIGEM), CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.

出版信息

Nanomedicine. 2020 Oct;29:102257. doi: 10.1016/j.nano.2020.102257. Epub 2020 Jun 28.

Abstract

Vaccine developmental strategies are utilizing antigens encapsulated in biodegradable polymeric nanoparticles. Here, we developed a Chlamydia nanovaccine (PLGA-rMOMP) by encapsulating its recombinant major outer membrane protein (rMOMP) in the extended-releasing and self-adjuvanting PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. PLGA-rMOMP was small (nanometer size), round and smooth, thermally stable, and exhibited a sustained release of rMOMP. Stimulation of mouse primary dendritic cells (DCs) with PLGA-rMOMP augmented endosome processing, induced Th1 cytokines (IL-6 and IL-12p40), and expression of MHC-II and co-stimulatory (CD40, CD80, and CD86) molecules. BALB/c mice immunized with PLGA-rMOMP produced enhanced CD4 T-cells-derived memory (CD44 CD62L), and effector (CD44 CD62L) phenotypes and functional antigen-specific serum IgG antibodies. In vivo biodistribution of PLGA-rMOMP revealed its localization within lymph nodes, suggesting migration from the injection site via DCs. Our data provide evidence that the PLGA (85:15) nanovaccine activates DCs and augments Chlamydia-specific rMOMP adaptive immune responses that are worthy of efficacy testing.

摘要

疫苗研发策略是利用包封在可生物降解的聚合物纳米颗粒中的抗原。在这里,我们通过将其重组主要外膜蛋白(rMOMP)包封在延长释放和自佐剂的 PLGA [聚(D,L-丙交酯-共-乙交酯)(85:15)]纳米颗粒中开发了一种衣原体纳米疫苗(PLGA-rMOMP)。PLGA-rMOMP 体积小(纳米级)、呈圆形且光滑,热稳定性好,并表现出 rMOMP 的持续释放。用 PLGA-rMOMP 刺激小鼠原代树突状细胞(DCs)增强了内体处理,诱导了 Th1 细胞因子(IL-6 和 IL-12p40)以及 MHC-II 和共刺激(CD40、CD80 和 CD86)分子的表达。用 PLGA-rMOMP 免疫的 BALB/c 小鼠产生了增强的 CD4 T 细胞衍生的记忆(CD44 CD62L)和效应(CD44 CD62L)表型以及功能性抗原特异性血清 IgG 抗体。PLGA-rMOMP 的体内生物分布显示其在淋巴结内的定位,表明其通过 DC 从注射部位迁移。我们的数据提供了证据表明,PLGA(85:15)纳米疫苗可激活 DC 并增强衣原体特异性 rMOMP 适应性免疫反应,值得进行疗效测试。

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