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

甘露糖修饰壳聚糖纳米颗粒沙门氏菌亚单位口服疫苗在肉鸡攻毒试验中诱导的免疫反应和功效

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

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.

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