Surface engineered polyanhydride-based oral Salmonella subunit nanovaccine for poultry

Sankar Renu,1,2,* Ashley D Markazi,3,* Santosh Dhakal,1,2 Yashavanth S Lakshmanappa,1,2 Suren R Gourapura,1,2 Revathi Shanmugasundaram,3 Sujata Senapati,4 Balaji Narasimhan,4 Ramesh K Selvaraj,5 Gourapura J Renukaradhya1,2 1Food Animal Health Research Program, Ohio Agricultural Research and Develop...

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Autores principales:	Renu S, Markazi AD, Dhakal S, Lakshmanappa YS, Gourapura SR, Shanmugasundaram R, Senapati S, Narasimhan B, Selvaraj RK, Renukaradhya GJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Salmonella antigens polyanhydride nanoparticles oral delivery ileum chickens Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8f073b95ebd049ae868e550f2937d7be
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spelling	oai:doaj.org-article:8f073b95ebd049ae868e550f2937d7be2021-12-02T01:16:19ZSurface engineered polyanhydride-based oral Salmonella subunit nanovaccine for poultry1178-2013https://doaj.org/article/8f073b95ebd049ae868e550f2937d7be2018-11-01T00:00:00Zhttps://www.dovepress.com/surface-engineered-polyanhydride-based-oral-salmonella-subunit-nanovac-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Sankar Renu,1,2,* Ashley D Markazi,3,* Santosh Dhakal,1,2 Yashavanth S Lakshmanappa,1,2 Suren R Gourapura,1,2 Revathi Shanmugasundaram,3 Sujata Senapati,4 Balaji Narasimhan,4 Ramesh K Selvaraj,5 Gourapura J Renukaradhya1,2 1Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH 44691, USA; 2Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA; 3Department of Animal Sciences, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH 44691, USA; 4Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA; 5Department of Poultry Science, University of Georgia, Athens, GA 30602, USA *These authors contributed equally to this work Purpose: Salmonellosis is a severe economic threat in poultry and a public health concern. Currently available vaccines are ineffective, and thus, developing effective oral Salmonella vaccine is warranted. Especially, a potent oral vaccine such as the mucoadhesive polyanhydride nanoparticle (PNP) protects the vaccine cargo and delivers to intestinal immune sites to elicit robust mucosal immunity and mitigate Salmonella colonization and shedding.Materials and methods: We designed a Salmonella subunit vaccine using PNP containing immunogenic Salmonella outer membrane proteins (OMPs) and flagellar (F) protein-entrapped and surface F-protein-coated PNPs (OMPs-F-PNPs) using a solvent displacement method. Using high-throughput techniques, we characterized the OMPs-F-PNPs physicochemical properties and analyzed its efficacy in layer birds vaccinated orally.Results: The candidate vaccine was resistant in acidic microenvironment and had ideal physicochemical properties for oral delivery in terms of particle size, charge, morphology, biocompatibility, and pH stability. In vitro, in vivo, and ex vivo studies showed that F-protein surface-anchored nanoparticles were better targeted to chicken immune cells in peripheral blood and splenocytes and intestinal Peyer’s patch sites. In layer chickens inoculated orally with OMPs-F-PNPs, substantially higher OMPs-specific IgG response and secretion of Th1 cytokine IFN-γ in the serum, enhanced CD8+/CD4+ cell ratio in spleen, and increased OMPs-specific lymphocyte proliferation were observed. OMPs-F-PNPs vaccination also upregulated the expression of toll-like receptor (TLR)-2 and -4, TGF-β, and IL-4 cytokines’ genes in chicken cecal tonsils (lymphoid tissues). Importantly, OMPs-F-PNPs vaccine cleared Salmonella cecal colonization in 33% of vaccinated birds.Conclusion: This pilot in vivo study demonstrated the targeted delivery of OMPs-F-PNPs to ileum mucosal immune sites of chickens and induced specific immune response to mitigate Salmonella colonization in intestines. Keywords: Salmonella antigens, polyanhydride nanoparticles, oral delivery, ileum, chickens Renu SMarkazi ADDhakal SLakshmanappa YSGourapura SRShanmugasundaram RSenapati SNarasimhan BSelvaraj RKRenukaradhya GJDove Medical PressarticleSalmonella antigenspolyanhydride nanoparticlesoral deliveryileumchickensMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 8195-8215 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Salmonella antigens polyanhydride nanoparticles oral delivery ileum chickens Medicine (General) R5-920
spellingShingle	Salmonella antigens polyanhydride nanoparticles oral delivery ileum chickens Medicine (General) R5-920 Renu S Markazi AD Dhakal S Lakshmanappa YS Gourapura SR Shanmugasundaram R Senapati S Narasimhan B Selvaraj RK Renukaradhya GJ Surface engineered polyanhydride-based oral Salmonella subunit nanovaccine for poultry
description	Sankar Renu,1,2,* Ashley D Markazi,3,* Santosh Dhakal,1,2 Yashavanth S Lakshmanappa,1,2 Suren R Gourapura,1,2 Revathi Shanmugasundaram,3 Sujata Senapati,4 Balaji Narasimhan,4 Ramesh K Selvaraj,5 Gourapura J Renukaradhya1,2 1Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH 44691, USA; 2Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA; 3Department of Animal Sciences, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH 44691, USA; 4Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA; 5Department of Poultry Science, University of Georgia, Athens, GA 30602, USA *These authors contributed equally to this work Purpose: Salmonellosis is a severe economic threat in poultry and a public health concern. Currently available vaccines are ineffective, and thus, developing effective oral Salmonella vaccine is warranted. Especially, a potent oral vaccine such as the mucoadhesive polyanhydride nanoparticle (PNP) protects the vaccine cargo and delivers to intestinal immune sites to elicit robust mucosal immunity and mitigate Salmonella colonization and shedding.Materials and methods: We designed a Salmonella subunit vaccine using PNP containing immunogenic Salmonella outer membrane proteins (OMPs) and flagellar (F) protein-entrapped and surface F-protein-coated PNPs (OMPs-F-PNPs) using a solvent displacement method. Using high-throughput techniques, we characterized the OMPs-F-PNPs physicochemical properties and analyzed its efficacy in layer birds vaccinated orally.Results: The candidate vaccine was resistant in acidic microenvironment and had ideal physicochemical properties for oral delivery in terms of particle size, charge, morphology, biocompatibility, and pH stability. In vitro, in vivo, and ex vivo studies showed that F-protein surface-anchored nanoparticles were better targeted to chicken immune cells in peripheral blood and splenocytes and intestinal Peyer’s patch sites. In layer chickens inoculated orally with OMPs-F-PNPs, substantially higher OMPs-specific IgG response and secretion of Th1 cytokine IFN-γ in the serum, enhanced CD8+/CD4+ cell ratio in spleen, and increased OMPs-specific lymphocyte proliferation were observed. OMPs-F-PNPs vaccination also upregulated the expression of toll-like receptor (TLR)-2 and -4, TGF-β, and IL-4 cytokines’ genes in chicken cecal tonsils (lymphoid tissues). Importantly, OMPs-F-PNPs vaccine cleared Salmonella cecal colonization in 33% of vaccinated birds.Conclusion: This pilot in vivo study demonstrated the targeted delivery of OMPs-F-PNPs to ileum mucosal immune sites of chickens and induced specific immune response to mitigate Salmonella colonization in intestines. Keywords: Salmonella antigens, polyanhydride nanoparticles, oral delivery, ileum, chickens
format	article
author	Renu S Markazi AD Dhakal S Lakshmanappa YS Gourapura SR Shanmugasundaram R Senapati S Narasimhan B Selvaraj RK Renukaradhya GJ
author_facet	Renu S Markazi AD Dhakal S Lakshmanappa YS Gourapura SR Shanmugasundaram R Senapati S Narasimhan B Selvaraj RK Renukaradhya GJ
author_sort	Renu S
title	Surface engineered polyanhydride-based oral Salmonella subunit nanovaccine for poultry
title_short	Surface engineered polyanhydride-based oral Salmonella subunit nanovaccine for poultry
title_full	Surface engineered polyanhydride-based oral Salmonella subunit nanovaccine for poultry
title_fullStr	Surface engineered polyanhydride-based oral Salmonella subunit nanovaccine for poultry
title_full_unstemmed	Surface engineered polyanhydride-based oral Salmonella subunit nanovaccine for poultry
title_sort	surface engineered polyanhydride-based oral salmonella subunit nanovaccine for poultry
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/8f073b95ebd049ae868e550f2937d7be
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Surface engineered polyanhydride-based oral Salmonella subunit nanovaccine for poultry

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