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Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine

文献类型： 外文期刊

作者： Han, Shulan 1 ; Ma, Wenyan 1 ; Jiang, Dawei 5 ; Sutherlin, Logan 6 ; Zhang, Jing 1 ; Lu, Yu 8 ; Huo, Nan 9 ; Chen, Zhao 10 ;

作者机构： 1.Chinese Acad Sci, Inst Proc Engn, Key Lab Green Proc & Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China

2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China

3.Jilin Univ, Sch Pharmaceut Sci, Changchun 130021, Peoples R China

4.Tianjin Univ Sci & Technol, Tianjin 300222, Peoples R China

5.Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Nucl Med, Wuhan 430022, Peoples R China

6.Univ Wisconsin, Dept Radiol, Madison, WI 53705 USA

7.Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USA

8.Jiangsu Acad Agr Sci, Inst Vet Immunol & Engn, Nanjing 210014, Peoples R China

9.Beijing Inst Biotechnol, Dept Genet Engn Lab, Beijing 100850, Peoples R China

10.Peking Univ First Hosp, Dept Nucl Med, Beijing 100034, Peoples R China

关键词： DDAB/PLGA; Nano-vaccine; DCs activation; p38 signaling pathway; Antigen transport

期刊名称：JOURNAL OF NANOBIOTECHNOLOGY （ 影响因子：10.435； 五年影响因子：9.151 ）

ISSN：

年卷期： 2021 年 19 卷 1 期

页码：

收录情况： SCI

摘要： Background: Poly(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles have potential applications as a vaccine adjuvant and delivery system due to its unique advantages as biodegradability and biocompatibility. Experimental: We fabricated cationic solid lipid nanoparticles using PLGA and dimethyl-dioctadecyl-ammonium bromide (DDAB), followed by loading of model antigen OVA (antigen ovalbumin, OVA(257-264)) to form an OVA@DDAB/PLGA nano-vaccine. And we investigated the intracellular signaling pathway in dendritic cells in vitro and antigen transport pathway and immune response in vivo mediated by an OVA@DDAB/PLGA nano-vaccine. Results: In vitro experiments revealed that the antigen uptake of BMDCs after nanovaccine incubation was two times higher than pure OVA or OVA@Al at 12 h. The BMDCs were well activated by p38 MAPK signaling pathway. Furthermore, the nano-vaccine induced antigen escape from lysosome into cytoplasm with 10 times increased cross-presentation activity than those of OVA or OVA@Al. Regarding the transport of antigen into draining lymph nodes (LNs), the nano-vaccine could rapidly transfer antigen to LNs by passive lymphatic drainage and active DC transport. The antigen(+) cells in inguinal/popliteal LNs for the nano-vaccine were increased over two folds comparing to OVA@Al and OVA at 12 h. Moreover, the antigen of nano-vaccine stayed in LNs for over 7 days, germinal center formation over two folds higher than those of OVA@Al and OVA. After immunization, the nano-vaccine induced a much higher ratio of IgG2c/IgG1 than OVA@Al. It also effectively activated CD4(+) T, CD8(+) T and B cells for immune memory with a strong cellular response. Conclusion: These results indicated that DDAB/PLGA NP was a potent platform to improve vaccine immunogenicity by p38 signaling pathway in BMDCs, enhancing transport of antigens to LNs, and higher immunity response.

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