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Surface engineered polyanhydride-based oral Salmonella subunit nanovaccine for poultry.

Authors :
Renu S
Markazi AD
Dhakal S
Lakshmanappa YS
Gourapura SR
Shanmugasundaram R
Senapati S
Narasimhan B
Selvaraj RK
Renukaradhya GJ
Source :
International journal of nanomedicine [Int J Nanomedicine] 2018 Nov 30; Vol. 13, pp. 8195-8215. Date of Electronic Publication: 2018 Nov 30 (Print Publication: 2018).
Publication Year :
2018

Abstract

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.<br />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.<br />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 <superscript>+</superscript> /CD4 <superscript>+</superscript> 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.<br />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.<br />Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Details

Language :
English
ISSN :
1178-2013
Volume :
13
Database :
MEDLINE
Journal :
International journal of nanomedicine
Publication Type :
Academic Journal
Accession number :
30555234
Full Text :
https://doi.org/10.2147/IJN.S185588