Induction of Robust Immune Responses by CpG-ODN-Loaded Hollow Polymeric Nanoparticles for Antiviral and Vaccine Applications in Chickens

Shu-Yi Lin,1 Bing-Yu Yao,2 Che-Ming Jack Hu,2,3 Hui-Wen Chen1,3 1Department of Veterinary Medicine, National Taiwan University, Taipei, Taiwan; 2Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; 3Research Center for Nanotechnology and Infectious Diseases, Taipei, TaiwanCorrespondenc...

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Autores principales:	Lin SY, Yao BY, Hu CMJ, Chen HW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	polymeric hollow nanoparticle cpg adjuvant antiviral response influenza virus infectious bronchitis virus vaccine Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/67618db94cf9425f9c6e0fc8ecf87aa1
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spelling	oai:doaj.org-article:67618db94cf9425f9c6e0fc8ecf87aa12021-12-02T10:26:48ZInduction of Robust Immune Responses by CpG-ODN-Loaded Hollow Polymeric Nanoparticles for Antiviral and Vaccine Applications in Chickens1178-2013https://doaj.org/article/67618db94cf9425f9c6e0fc8ecf87aa12020-05-01T00:00:00Zhttps://www.dovepress.com/induction-of-robust-immune-responses-by-cpg-odn-loaded-hollow-polymeri-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Shu-Yi Lin,1 Bing-Yu Yao,2 Che-Ming Jack Hu,2,3 Hui-Wen Chen1,3 1Department of Veterinary Medicine, National Taiwan University, Taipei, Taiwan; 2Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; 3Research Center for Nanotechnology and Infectious Diseases, Taipei, TaiwanCorrespondence: Hui-Wen ChenDepartment of Veterinary Medicine, National Taiwan University, 1 Sec 4 Roosevelt Road, Taipei 10617, TaiwanTel +886 2 33669450Email winnichen@ntu.edu.twBackground: Poultry vaccine has limited choices of adjuvants and is facing severe threat of infectious diseases due to ineffective of widely used commercial vaccines. Thus, development of novel adjuvant that offers safe and effective immunity is of urgent need.Materials and Methods: The present research engineers a novel chicken adjuvant with potent immune-potentiating capability by incorporating avian toll-like receptor 21 (TLR21) agonist CpG ODN 2007 with a poly(lactic-co-glycolic acid) (PLGA)-based hollow nanoparticle platform (CpG-NP), which subsequently assessed ex vivo and in vivo.Results: CpG-NPs with an average diameter of 164 nm capable of sustained release of CpG for up to 96 hours were successfully prepared. With the ex vivo model of chicken bone marrow-derived dendritic cells (chBMDCs), CpG-NP was engulfed effectively and found to induce DC maturation, promoting dendrite formation and upregulation of CD40, CD80 and CCR7. In addition to enhanced expression of IL-1β, IL-6, IL-12 and IFN-γ, 53/84 immune-related genes were found to be stimulated in CpG-NP-treated chBMDCs, whereas only 39 of such genes were stimulated in free CpG-treated cells. These upregulated genes suggest immune skewing toward T helper cell 1 bias and evidence of improved mucosal immunity upon vaccination with the CpG-NP. The CpG-NP-treated chBMDCs showed protective effects to DF-1 cells against avian influenza virus H6N1 infection. Upon subsequent coupling with infectious bronchitis virus subunit antigen administration, chickens were immunostimulated to acquire higher humoral immune response and protective response against viral challenge.Conclustion: This work presents a novel hollow CpG-NP formulation, demonstrating effective and long-lasting immunostimulatory ability ex vivo and in vivo for chickens, as systemically compared to free CpG. This enhanced immune stimulation benefits from high stability and controlled release of internal component of nanoparticles that improve cellular delivery, lymphoid organ targeting and sustainable DC activation. CpG-NP has broad application potential in antiviral and vaccine development.Keywords: polymeric hollow nanoparticle, CpG, adjuvant, antiviral response, influenza virus, infectious bronchitis virus, vaccineLin SYYao BYHu CMJChen HWDove Medical Pressarticlepolymeric hollow nanoparticlecpgadjuvantantiviral responseinfluenza virusinfectious bronchitis virusvaccineMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 3303-3318 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	polymeric hollow nanoparticle cpg adjuvant antiviral response influenza virus infectious bronchitis virus vaccine Medicine (General) R5-920
spellingShingle	polymeric hollow nanoparticle cpg adjuvant antiviral response influenza virus infectious bronchitis virus vaccine Medicine (General) R5-920 Lin SY Yao BY Hu CMJ Chen HW Induction of Robust Immune Responses by CpG-ODN-Loaded Hollow Polymeric Nanoparticles for Antiviral and Vaccine Applications in Chickens
description	Shu-Yi Lin,1 Bing-Yu Yao,2 Che-Ming Jack Hu,2,3 Hui-Wen Chen1,3 1Department of Veterinary Medicine, National Taiwan University, Taipei, Taiwan; 2Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; 3Research Center for Nanotechnology and Infectious Diseases, Taipei, TaiwanCorrespondence: Hui-Wen ChenDepartment of Veterinary Medicine, National Taiwan University, 1 Sec 4 Roosevelt Road, Taipei 10617, TaiwanTel +886 2 33669450Email winnichen@ntu.edu.twBackground: Poultry vaccine has limited choices of adjuvants and is facing severe threat of infectious diseases due to ineffective of widely used commercial vaccines. Thus, development of novel adjuvant that offers safe and effective immunity is of urgent need.Materials and Methods: The present research engineers a novel chicken adjuvant with potent immune-potentiating capability by incorporating avian toll-like receptor 21 (TLR21) agonist CpG ODN 2007 with a poly(lactic-co-glycolic acid) (PLGA)-based hollow nanoparticle platform (CpG-NP), which subsequently assessed ex vivo and in vivo.Results: CpG-NPs with an average diameter of 164 nm capable of sustained release of CpG for up to 96 hours were successfully prepared. With the ex vivo model of chicken bone marrow-derived dendritic cells (chBMDCs), CpG-NP was engulfed effectively and found to induce DC maturation, promoting dendrite formation and upregulation of CD40, CD80 and CCR7. In addition to enhanced expression of IL-1β, IL-6, IL-12 and IFN-γ, 53/84 immune-related genes were found to be stimulated in CpG-NP-treated chBMDCs, whereas only 39 of such genes were stimulated in free CpG-treated cells. These upregulated genes suggest immune skewing toward T helper cell 1 bias and evidence of improved mucosal immunity upon vaccination with the CpG-NP. The CpG-NP-treated chBMDCs showed protective effects to DF-1 cells against avian influenza virus H6N1 infection. Upon subsequent coupling with infectious bronchitis virus subunit antigen administration, chickens were immunostimulated to acquire higher humoral immune response and protective response against viral challenge.Conclustion: This work presents a novel hollow CpG-NP formulation, demonstrating effective and long-lasting immunostimulatory ability ex vivo and in vivo for chickens, as systemically compared to free CpG. This enhanced immune stimulation benefits from high stability and controlled release of internal component of nanoparticles that improve cellular delivery, lymphoid organ targeting and sustainable DC activation. CpG-NP has broad application potential in antiviral and vaccine development.Keywords: polymeric hollow nanoparticle, CpG, adjuvant, antiviral response, influenza virus, infectious bronchitis virus, vaccine
format	article
author	Lin SY Yao BY Hu CMJ Chen HW
author_facet	Lin SY Yao BY Hu CMJ Chen HW
author_sort	Lin SY
title	Induction of Robust Immune Responses by CpG-ODN-Loaded Hollow Polymeric Nanoparticles for Antiviral and Vaccine Applications in Chickens
title_short	Induction of Robust Immune Responses by CpG-ODN-Loaded Hollow Polymeric Nanoparticles for Antiviral and Vaccine Applications in Chickens
title_full	Induction of Robust Immune Responses by CpG-ODN-Loaded Hollow Polymeric Nanoparticles for Antiviral and Vaccine Applications in Chickens
title_fullStr	Induction of Robust Immune Responses by CpG-ODN-Loaded Hollow Polymeric Nanoparticles for Antiviral and Vaccine Applications in Chickens
title_full_unstemmed	Induction of Robust Immune Responses by CpG-ODN-Loaded Hollow Polymeric Nanoparticles for Antiviral and Vaccine Applications in Chickens
title_sort	induction of robust immune responses by cpg-odn-loaded hollow polymeric nanoparticles for antiviral and vaccine applications in chickens
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/67618db94cf9425f9c6e0fc8ecf87aa1
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Induction of Robust Immune Responses by CpG-ODN-Loaded Hollow Polymeric Nanoparticles for Antiviral and Vaccine Applications in Chickens

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