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A nanovaccine formulation of Chlamydia recombinant MOMP encapsulated in PLGA 85:15 nanoparticles augments CD4+ effector (CD44high CD62Llow) and memory (CD44high CD62Lhigh) T-cells in immunized mice.
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 5.4 ) Pub Date : 2020-06-28 , DOI: 10.1016/j.nano.2020.102257
Rajnish Sahu 1 , Saurabh Dixit 1 , Richa Verma 1 , Skyla A Duncan 1 , Mamie T Coats 1 , Guillermo H Giambartolomei 2 , Shree R Singh 1 , Vida A Dennis 1
Affiliation  

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 (CD44high CD62Lhigh), and effector (CD44high CD62Llow) 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.



中文翻译:

包裹在 PLGA 85:15 纳米颗粒中的衣原体重组 MOMP 纳米疫苗制剂可增强免疫小鼠中的 CD4+ 效应 (CD44high CD62Llow) 和记忆 (CD44high CD62Lhigh) T 细胞。

疫苗开发策略正在利用封装在可生物降解的聚合物纳米颗粒中的抗原。在这里,我们开发了一种衣原体纳米疫苗 (PLGA-rMOMP),方法是将其重组主要外膜蛋白 (rMOMP) 封装在缓释和自辅助 PLGA [聚 (D, L-丙交酯-共-乙交酯) (85:15) 中)]纳米粒子。PLGA-rMOMP 体积小(纳米级)、圆润光滑、热稳定,并且可以缓释 rMOMP。用 PLGA-rMOMP 刺激小鼠原代树突状细胞 (DC) 增强内体加工,诱导 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 小鼠产生增强的 CD4 + T 细胞衍生记忆(CD44CD62L)和效应子(CD44CD62L)表型和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,表明通过DC 从注射部位迁移。我们的数据提供的证据表明,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,这值得进行功效测试。

更新日期:2020-07-24
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