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

Abstract 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 dimeth...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shulan Han, Wenyan Ma, Dawei Jiang, Logan Sutherlin, Jing Zhang, Yu Lu, Nan Huo, Zhao Chen, Jonathan W. Engle, Yanping Wang, Xiaojie Xu, Lei Kang, Weibo Cai, Lianyan Wang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	DDAB/PLGA Nano-vaccine DCs activation p38 signaling pathway Antigen transport Biotechnology TP248.13-248.65 Medical technology R855-855.5
Acceso en línea:	https://doaj.org/article/c3653e845d0046e18d6e6664078eb149
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c3653e845d0046e18d6e6664078eb149
record_format	dspace
spelling	oai:doaj.org-article:c3653e845d0046e18d6e6664078eb1492021-11-28T12:26:33ZIntracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine10.1186/s12951-021-01116-81477-3155https://doaj.org/article/c3653e845d0046e18d6e6664078eb1492021-11-01T00:00:00Zhttps://doi.org/10.1186/s12951-021-01116-8https://doaj.org/toc/1477-3155Abstract 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 AbstractShulan HanWenyan MaDawei JiangLogan SutherlinJing ZhangYu LuNan HuoZhao ChenJonathan W. EngleYanping WangXiaojie XuLei KangWeibo CaiLianyan WangBMCarticleDDAB/PLGANano-vaccineDCs activationp38 signaling pathwayAntigen transportBiotechnologyTP248.13-248.65Medical technologyR855-855.5ENJournal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	DDAB/PLGA Nano-vaccine DCs activation p38 signaling pathway Antigen transport Biotechnology TP248.13-248.65 Medical technology R855-855.5
spellingShingle	DDAB/PLGA Nano-vaccine DCs activation p38 signaling pathway Antigen transport Biotechnology TP248.13-248.65 Medical technology R855-855.5 Shulan Han Wenyan Ma Dawei Jiang Logan Sutherlin Jing Zhang Yu Lu Nan Huo Zhao Chen Jonathan W. Engle Yanping Wang Xiaojie Xu Lei Kang Weibo Cai Lianyan Wang Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine
description	Abstract 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
format	article
author	Shulan Han Wenyan Ma Dawei Jiang Logan Sutherlin Jing Zhang Yu Lu Nan Huo Zhao Chen Jonathan W. Engle Yanping Wang Xiaojie Xu Lei Kang Weibo Cai Lianyan Wang
author_facet	Shulan Han Wenyan Ma Dawei Jiang Logan Sutherlin Jing Zhang Yu Lu Nan Huo Zhao Chen Jonathan W. Engle Yanping Wang Xiaojie Xu Lei Kang Weibo Cai Lianyan Wang
author_sort	Shulan Han
title	Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine
title_short	Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine
title_full	Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine
title_fullStr	Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine
title_full_unstemmed	Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine
title_sort	intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an ova@ddab/plga nano-vaccine
publisher	BMC
publishDate	2021
url	https://doaj.org/article/c3653e845d0046e18d6e6664078eb149
work_keys_str_mv	AT shulanhan intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine AT wenyanma intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine AT daweijiang intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine AT logansutherlin intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine AT jingzhang intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine AT yulu intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine AT nanhuo intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine AT zhaochen intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine AT jonathanwengle intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine AT yanpingwang intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine AT xiaojiexu intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine AT leikang intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine AT weibocai intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine AT lianyanwang intracellularsignalingpathwayindendriticcellsandantigentransportpathwayinvivomediatedbyanovaddabplgananovaccine
_version_	1718407981153910784

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

Ejemplares similares