Mannose-Modified Chitosan-Nanoparticle-Based Salmonella Subunit OralVaccine-Induced Immune Response and Efficacy in a Challenge Trial in Broilers.

Yi Han,Gourapura J Renukaradhya,Veerupaxagouda Patil,Ninoshkaly Feliciano-Ruiz,Sankar Renu,Jennifer Schrock,Ramesh Selvaraj

doi:10.3390/vaccines8020299

Yi Han, Gourapura J Renukaradhya + Show 5 more

Open Access

https://doi.org/10.3390/vaccines8020299

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Journal: Vaccines	Publication Date: Jun 11, 2020
Citations: 16	License type: CC BY 4.0

Affiliation: The Ohio State University, University of Georgia

Abstract

Controlling Salmonella enterica serovar Enteritidis (SE) infection in broilers is a huge challenge. In this study, our objective was to improve the efficacy of a chitosan nanoparticle (CS)-based Salmonella subunit vaccine for SE, containing immunogenic outer membrane proteins (OMP) and flagellin (FLA), called the CS(OMP+FLA) vaccine, by surface conjugating it with mannose to target dendritic cells, and comparing the immune responses and efficacy with a commercial live Salmonella vaccine in broilers. The CS(OMP+FLA)-based vaccines were administered orally at age 3 days and as a booster dose after three weeks, and the broilers were challenged with SE at 5 weeks of age. Birds were sacrificed 10 days post-challenge and it was observed that CS(OMP+FLA) vaccine surface conjugated with both mannose and FLA produced the greatest SE reduction, by over 1 log10 colony forming unit per gram of the cecal content, which was comparable to a commercial live vaccine. Immunologically, specific mucosal antibody responses were enhanced by FLA-surface-coated CS(OMP+FLA) vaccine, and mannose-bound CS(OMP+FLA) improved the cellular immune response. In addition, increased mRNA expression of Toll-like receptors and cytokine was observed in CS(OMP+FLA)-based-vaccinated birds. The commercial live vaccine failed to induce any such substantial immune response, except that they had a slightly improved T helper cell frequency. Our data suggest that FLA-coated and mannose-modified CS(OMP+FLA) vaccine induced robust innate and adaptive cell-mediated immune responses and substantially reduced the Salmonella load in the intestines of broilers.

Highlights

Salmonella enterica serovar Enteritidis (SE) is a Gram-negative bacterium that causes the majority of foodborne illness associated with broilers and is responsible for major economic losses to theU.S poultry industry [1]
Commercial live Salmonella vaccines are unsafe as the live vaccine strains are potentially released into the environment and contaminate the human food chain [4]
Broiler chickens were purchased from a commercial hatchery for testing the efficacy of our candidate oral-delivered chitosan nanoparticle (CS)-based Salmonella subunit vaccine formulations and compared that with a commercial live vaccine (Poulvac® Salmonella typhimurium (ST), Kalamazoo, MI, USA) administered orally on the same day

Summary

Introduction

Salmonella enterica serovar Enteritidis (SE) is a Gram-negative bacterium that causes the majority of foodborne illness associated with broilers and is responsible for major economic losses to theU.S poultry industry [1]. Salmonella contamination accounted for the greatest number of FDA-regulated food recalls during 2003 through 2011 [3]. Vaccines 2020, 8, 299 humans can be substantially decreased by reducing Salmonella colonization in poultry. There are limited commercially available Salmonella vaccines for use in broilers, and none of them provides protective immunity until slaughter. Commercial live Salmonella vaccines are unsafe as the live vaccine strains (attenuated by natural selection or genetic engineering) are potentially released into the environment and contaminate the human food chain [4]. Due to a lack of effective vaccines and safety reasons, less than 1% of broilers receive a live Salmonella spray vaccine once [5], and FDA regulations prohibit its use within 21 days of slaughter

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