Co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-co-glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen

Xiaojing Dai, Jintian He, Ruxia Zhang, Guanghao Wu, Fangfang Xiong, Baohua Zhao College of Life Science, Hebei Normal University, Shijiazhuang City, Hebei Province, People’s Republic of China Abstract: The aim of the present work was to investigate the synergistic effect between toll-lik...

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Autores principales:	Dai X, He J, Zhang R, Wu G, Xiong F, Zhao B
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Toll-like receptor polyinosinic:polycytidylic acid flagellin hepatitis B surface antigen PLGA microparticles Intranasal vaccination Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d3d4ccd1697f423f8e8a306d5153fbd2
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spelling	oai:doaj.org-article:d3d4ccd1697f423f8e8a306d5153fbd22021-12-02T05:10:44ZCo-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-co-glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen1178-2013https://doaj.org/article/d3d4ccd1697f423f8e8a306d5153fbd22017-09-01T00:00:00Zhttps://www.dovepress.com/co-delivery-of-polyinosinicpolycytidylic-acid-and-flagellin-by-polylac-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiaojing Dai, Jintian He, Ruxia Zhang, Guanghao Wu, Fangfang Xiong, Baohua Zhao College of Life Science, Hebei Normal University, Shijiazhuang City, Hebei Province, People’s Republic of China Abstract: The aim of the present work was to investigate the synergistic effect between toll-like receptor (TLR) 3 ligand polyinosinic:polycytidylic acid (pI:C) and TLR5 ligand flagellin (FLN) on immune responses induced by nasally delivered hepatitis B virus surface antigen (HBsAg). Mannan and chitosan oligosaccharide-modified, pH-responsive poly(lactic-co-glycolic acid) (MC-PLGA) microparticles (MPs) containing HBsAg, FLN, pI:C or both ligands were prepared with a double-emulsion method. In vitro uptake experiments show that cellular uptake of MC-PLGA MPs by macrophages was through energy-dependent, receptor-mediated endocytosis mechanism. After uptake of MPs by macrophages, MC-PLGA MPs existed both in the endosome and in the cytoplasm. FLN and pI:C in solution or MP formulation could synergize to activate macrophages and induce higher pro-inflammatory cytokines interleukin (IL)-6, IL-12, interferon-γ and anti-inflammatory cytokines IL-10 compared to single TLR ligand (P<0.05). In vivo immunogenicity studies indicated that co-delivery of FLN and pI:C within MC-PLGA MPs synergistically induced higher serum anti-HBsAg IgG levels and Th1 cytokine levels compared with MC-PLGA MPs encapsulated single TLR ligand plus MPs encapsulated HBsAg (P<0.05). These results suggest that synergic TLR3 and TLR5 stimulation might be a promising novel tool for nasally delivered HBsAg. Keywords: toll-like receptor, polyinosinic:polycytidylic acid, flagellin, hepatitis B surface antigen, PLGA MPs, intranasal vaccinationDai XHe JZhang RWu GXiong FZhao BDove Medical PressarticleToll-like receptorpolyinosinic:polycytidylic acidflagellinhepatitis B surface antigenPLGA microparticlesIntranasal vaccinationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 6617-6632 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Toll-like receptor polyinosinic:polycytidylic acid flagellin hepatitis B surface antigen PLGA microparticles Intranasal vaccination Medicine (General) R5-920
spellingShingle	Toll-like receptor polyinosinic:polycytidylic acid flagellin hepatitis B surface antigen PLGA microparticles Intranasal vaccination Medicine (General) R5-920 Dai X He J Zhang R Wu G Xiong F Zhao B Co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-co-glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen
description	Xiaojing Dai, Jintian He, Ruxia Zhang, Guanghao Wu, Fangfang Xiong, Baohua Zhao College of Life Science, Hebei Normal University, Shijiazhuang City, Hebei Province, People’s Republic of China Abstract: The aim of the present work was to investigate the synergistic effect between toll-like receptor (TLR) 3 ligand polyinosinic:polycytidylic acid (pI:C) and TLR5 ligand flagellin (FLN) on immune responses induced by nasally delivered hepatitis B virus surface antigen (HBsAg). Mannan and chitosan oligosaccharide-modified, pH-responsive poly(lactic-co-glycolic acid) (MC-PLGA) microparticles (MPs) containing HBsAg, FLN, pI:C or both ligands were prepared with a double-emulsion method. In vitro uptake experiments show that cellular uptake of MC-PLGA MPs by macrophages was through energy-dependent, receptor-mediated endocytosis mechanism. After uptake of MPs by macrophages, MC-PLGA MPs existed both in the endosome and in the cytoplasm. FLN and pI:C in solution or MP formulation could synergize to activate macrophages and induce higher pro-inflammatory cytokines interleukin (IL)-6, IL-12, interferon-γ and anti-inflammatory cytokines IL-10 compared to single TLR ligand (P<0.05). In vivo immunogenicity studies indicated that co-delivery of FLN and pI:C within MC-PLGA MPs synergistically induced higher serum anti-HBsAg IgG levels and Th1 cytokine levels compared with MC-PLGA MPs encapsulated single TLR ligand plus MPs encapsulated HBsAg (P<0.05). These results suggest that synergic TLR3 and TLR5 stimulation might be a promising novel tool for nasally delivered HBsAg. Keywords: toll-like receptor, polyinosinic:polycytidylic acid, flagellin, hepatitis B surface antigen, PLGA MPs, intranasal vaccination
format	article
author	Dai X He J Zhang R Wu G Xiong F Zhao B
author_facet	Dai X He J Zhang R Wu G Xiong F Zhao B
author_sort	Dai X
title	Co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-co-glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen
title_short	Co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-co-glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen
title_full	Co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-co-glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen
title_fullStr	Co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-co-glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen
title_full_unstemmed	Co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-co-glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen
title_sort	co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-co-glycolic acid) mps synergistically enhances immune response elicited by intranasally delivered hepatitis b surface antigen
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/d3d4ccd1697f423f8e8a306d5153fbd2
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Co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic-co-glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen

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