Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine.
Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine.
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OVA@DDAB/PLGA纳米疫苗介导的树突状细胞内信号通路和体内抗原转运通路
DOI：
10.1186/s12951-021-01116-8
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发表时间：
2021-11-27
影响因子：
10.2
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Han S;Ma W;Jiang D;Sutherlin L;Zhang J;Lu Y;Huo N;Chen Z;Engle JW;Wang Y;Xu X;Kang L;Cai W;Wang L
背景
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, OVA257-264) 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.
Graphical Abstract
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影响因子：
--
作者：
Kim WS;Kim JS;Cha SB;Kim H;Kwon KW;Kim SJ;Han SJ;Choi SY;Cho SN;Park JH;Shin SJ
通讯作者：
Shin SJ
影响因子：
20.3
作者：
Hsieh, MH;Korngold, R
通讯作者：
Korngold, R
影响因子：
5.5
作者：
Verma, Shivani;Sugadev, Ragumani;Bansal, Anju
通讯作者：
Bansal, Anju
DOI：
10.1155/2012/735396
发表时间：
2012
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Chou NT;Cheng CF;Wu HC;Lai CP;Lin LT;Pan IH;Ko CH
通讯作者：
Ko CH
影响因子：
5.8
作者：
Avgoustakis, K;Beletsi, A;Ithakissios, DS
通讯作者：
Ithakissios, DS