Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague

Shih-shiung Huang,1 I-Hsun Li,2,3 Po-da Hong,1 Ming-kung Yeh1,2,41Biomedical Engineering Program, Graduate Institute of Engineering, Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, Republic of China; 2School of Pharmacy, 3Depart...

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Autores principales:	Huang SS, Li IH, Hong PD, Yeh MK
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
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spelling	oai:doaj.org-article:0ed391bbed9f4c40a2b0a38f805b84c12021-12-02T00:24:24ZDevelopment of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague1178-2013https://doaj.org/article/0ed391bbed9f4c40a2b0a38f805b84c12014-02-01T00:00:00Zhttp://www.dovepress.com/development-of-yersinia-pestis-f1-antigen-loaded-microspheres-vaccine--a15737https://doaj.org/toc/1178-2013 Shih-shiung Huang,1 I-Hsun Li,2,3 Po-da Hong,1 Ming-kung Yeh1,2,41Biomedical Engineering Program, Graduate Institute of Engineering, Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, Republic of China; 2School of Pharmacy, 3Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 4Food and Drug Administration, Ministry of Health and Welfare, Taipei, Taiwan, Republic of ChinaAbstract: Yersinia pestis F1 antigen-loaded poly(DL-lactide-co-glycolide)/polyethylene glycol (PEG) (PLGA/PEG) microspheres were produced using a water-in-oil-in-water emulsion/solvent extraction technique and assayed for their percent yield, entrapment efficiency, surface morphology, particle size, zeta potential, in vitro release properties, and in vivo animal protect efficacy. The Y. pestis F1 antigen-loaded microspheres (mean particle size 3.8 µm) exhibited a high loading capacity (4.5% w/w), yield (85.2%), and entrapment efficiency (38.1%), and presented a controlled in vitro release profile with a low initial burst (18.5%), then continued to release Y. pestis F1 antigen over 70 days. The distribution (%) of Y. pestis F1 on the microspheres surface, outer layer, and core was 3.1%, 28.9%, and 60.7%, respectively. A steady release rate was noticed to be 0.55 µg Y. pestis F1 antigen/mg microspheres/day of Y. pestis F1 antigen release maintained for 42 days. The cumulative release amount at the 1st, 28th, and 42nd days was 8.2, 26.7, and 31.0 µg Y. pestis F1 antigen/mg microspheres, respectively. The 100 times median lethal dose 50% (LD50) of Y. pestis Yokohama-R strain by intraperitoneal injection challenge in mice test, in which mice received one dose of 40 µg F1 antigen content of PLGA/PEG microspheres, F1 antigen in Al(OH)3, and in comparison with F1 antigen in Al(OH)3 vaccine in two doses, was evaluated after given by subcutaneous immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with one dose of F1 antigen-loaded PLGA/PEG microspheres, and two doses of F1 antigen in Al(OH)3 vaccine (100%). In vivo vaccination studies also demonstrated that F1 vaccines microspheres had a protective ability; its steady-state IgG immune protection in mice plasma dramatic increased from 2 weeks (18,764±3,124) to 7 weeks (126,468±19,176) after vaccination. These findings strongly suggest that F1-antigen loaded microspheres vaccine offer a new therapeutic strategy in optimizing the vaccine incorporation and delivery properties of these potential vaccine targeting carriers.Keywords: PLGA, immunological, protective responsesHuang SSLi IHHong PDYeh MKDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 813-822 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Huang SS Li IH Hong PD Yeh MK Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague
description	Shih-shiung Huang,1 I-Hsun Li,2,3 Po-da Hong,1 Ming-kung Yeh1,2,41Biomedical Engineering Program, Graduate Institute of Engineering, Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, Republic of China; 2School of Pharmacy, 3Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 4Food and Drug Administration, Ministry of Health and Welfare, Taipei, Taiwan, Republic of ChinaAbstract: Yersinia pestis F1 antigen-loaded poly(DL-lactide-co-glycolide)/polyethylene glycol (PEG) (PLGA/PEG) microspheres were produced using a water-in-oil-in-water emulsion/solvent extraction technique and assayed for their percent yield, entrapment efficiency, surface morphology, particle size, zeta potential, in vitro release properties, and in vivo animal protect efficacy. The Y. pestis F1 antigen-loaded microspheres (mean particle size 3.8 µm) exhibited a high loading capacity (4.5% w/w), yield (85.2%), and entrapment efficiency (38.1%), and presented a controlled in vitro release profile with a low initial burst (18.5%), then continued to release Y. pestis F1 antigen over 70 days. The distribution (%) of Y. pestis F1 on the microspheres surface, outer layer, and core was 3.1%, 28.9%, and 60.7%, respectively. A steady release rate was noticed to be 0.55 µg Y. pestis F1 antigen/mg microspheres/day of Y. pestis F1 antigen release maintained for 42 days. The cumulative release amount at the 1st, 28th, and 42nd days was 8.2, 26.7, and 31.0 µg Y. pestis F1 antigen/mg microspheres, respectively. The 100 times median lethal dose 50% (LD50) of Y. pestis Yokohama-R strain by intraperitoneal injection challenge in mice test, in which mice received one dose of 40 µg F1 antigen content of PLGA/PEG microspheres, F1 antigen in Al(OH)3, and in comparison with F1 antigen in Al(OH)3 vaccine in two doses, was evaluated after given by subcutaneous immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with one dose of F1 antigen-loaded PLGA/PEG microspheres, and two doses of F1 antigen in Al(OH)3 vaccine (100%). In vivo vaccination studies also demonstrated that F1 vaccines microspheres had a protective ability; its steady-state IgG immune protection in mice plasma dramatic increased from 2 weeks (18,764±3,124) to 7 weeks (126,468±19,176) after vaccination. These findings strongly suggest that F1-antigen loaded microspheres vaccine offer a new therapeutic strategy in optimizing the vaccine incorporation and delivery properties of these potential vaccine targeting carriers.Keywords: PLGA, immunological, protective responses
format	article
author	Huang SS Li IH Hong PD Yeh MK
author_facet	Huang SS Li IH Hong PD Yeh MK
author_sort	Huang SS
title	Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague
title_short	Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague
title_full	Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague
title_fullStr	Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague
title_full_unstemmed	Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague
title_sort	development of yersinia pestis f1 antigen-loaded microspheres vaccine against plague
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/0ed391bbed9f4c40a2b0a38f805b84c1
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Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague

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