Engineering of Targeted Mucoadhesive Chitosan Based Salmonella Nanovaccine for Oral Delivery in Poultry

Abstract

Abstract Salmonellosis in poultry is a serious economic burden. The major concern is the public health hazard by consumption of salmonella contaminated poultry meat and egg. Currently used salmonella vaccines are ineffective in combating the Salmonellosis of chicken thus warranting the need of a potent vaccine, especially an oral vaccine that can elicit robust local intestinal immunity. Biodegradable and biocompatible natural polymers are FDA approved vehicles for vaccine delivery. We prepared a candidate subunit chitosan nanoparticle vaccine containing the immunogenic outer membrane proteins (OMPs) and flagellar (F) protein of salmonella, and surface decorated with F-protein (OMPs-F-CS NPs). Physicochemical and biocompatibility properties of OMPs-F-CS NPs were studied in detail including its stability in stomach pH conditions. Salmonella targets the microfold (M) cells in the ileum Peyer’s patches (PPs) of chicken. We designed the oral OMPs-F-CS NPs vaccine to target ileal PPs to induce specific local intestinal immunity, and demonstrated that by ex vivo and in vivo studies. Layer chickens vaccinated orally with OMPs-F-CS NPs had significantly higher OMPs- specific intestinal mucosal antibody and OMPs-specific lymphocytes proliferation responses. Further, OMPs-F-CS NPs vaccination upregulated the expression of toll-like receptor (TLR) -2, TLR-4, IFN-g, IL-4 and GATA-3 mRNA levels in cecal tonsils of birds. In conclusion, we engineered chitosan based oral salmonella nanovaccine targeting intestinal PPs immune cells of birds, and demonstrated its ability to induce antigen specific mucosal antibody and T cell responses. Thus, our candidate oral salmonella vaccine has the potential to mitigate Salmonellosis in poultry.