Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine
Han,Shulan1,2,3; Ma,Wenyan1,2,4; Jiang,Dawei5; Sutherlin,Logan6; Zhang,Jing1,2; Lu,Yu7; Huo,Nan8; Chen,Zhao9; Engle,Jonathan W.6; Wang,Yanping4; Xu,Xiaojie8; Kang,Lei9; Cai,Weibo6; Wang,Lianyan1,2
Source PublicationJournal of Nanobiotechnology
AbstractAbstractBackgroundPoly(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.ExperimentalWe 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.ResultsIn 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.ConclusionThese 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
KeywordDDAB/PLGA Nano-vaccine DCs activation p38 signaling pathway Antigen transport
WOS IDBMC:10.1186/s12951-021-01116-8
PublisherBioMed Central
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Document Type期刊论文
Corresponding AuthorWang,Yanping; Xu,Xiaojie; Kang,Lei; Cai,Weibo; Wang,Lianyan
Affiliation1.Chinese Academy of Sciences; Key Laboratory of Green Process and Engineering, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering
2.University of Chinese Academy of Sciences
3.Jilin University; School of Pharmaceutical Sciences
4.Tianjin University of Science and Technology
5.Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Department of Nuclear Medicine
6.University of Wisconsin - Madison; Departments of Radiology and Medical Physics
7.Jiangsu Academy of Agricultural Sciences; Institute of Veterinary Immunology &Engineering
8.Beijing Institute of Biotechnology; Department of Genetic Engineering Laboratory
9.Peking University First Hospital; Department of Nuclear Medicine
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GB/T 7714
Han,Shulan,Ma,Wenyan,Jiang,Dawei,et al. Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine[J]. Journal of Nanobiotechnology,2021,19(1).
APA Han,Shulan.,Ma,Wenyan.,Jiang,Dawei.,Sutherlin,Logan.,Zhang,Jing.,...&Wang,Lianyan.(2021).Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine.Journal of Nanobiotechnology,19(1).
MLA Han,Shulan,et al."Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine".Journal of Nanobiotechnology 19.1(2021).
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