title: Outer membrane vesicles derived from Salmonella Typhimurium mutants with truncated LPS induce cross-protective immune responses against infection of Salmonella enterica serovars in the mouse model.
abstract: Salmonella enterica cause diarrheal and systemic diseases and are of considerable concern worldwide. Vaccines that are cross-protective against multiple serovars could provide effective control of Salmonella-mediated diseases. Bacteria-derived outer membrane vesicles (OMVs) are highly immunogenic and are capable of eliciting protective immune responses. Alterations in lipopolysaccharide (LPS) length can result in outer membrane remodeling and composition of outer membrane proteins (OMPs) changing. In this study, we investigated the impact of truncated LPS on both the production and immunogenicity of Salmonella OMVs, including the ability of OMVs to elicit cross-protection against challenge by heterologous Salmonella strains. We found that mutations in waaJ and rfbP enhanced vesiculation, while mutations in waaC, waaF and waaG inhibited this process. Animal experiments indicated that OMVs from waaC, rfaH and rfbP mutants induced stronger serum immune responses compared to OMVs from the parent strain, while all elicited protective responses against the wild-type S. Typhimurium challenge. Furthermore, intranasal or intraperitoneal immunization with OMVs derived from the waaC and rfbP mutants elicited significantly higher cross-reactive IgG responses and provided enhanced cross-protection against S. Choleraesuis and S. Enteritidis challenge than the wild-type OMVs. These results indicate that truncated-LPS OMVs are capable of conferring cross protection against multiple serotypes of Salmonella infection.
authors: Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, 611130 Chengdu, China; Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287-5401, USA; Department of Medical Microbiology, School of Medicine, Nanchang University, 330006 Nanchang, China.
authors: Qiong
authors: Q
authors: Liu
authors: Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, 611130 Chengdu, China.
authors: Qing
authors: Q
authors: Liu
authors: Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, 611130 Chengdu, China.
authors: Jie
authors: J
authors: Yi
authors: Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, 611130 Chengdu, China.
authors: Kang
authors: K
authors: Liang
authors: Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, 611130 Chengdu, China.
authors: Tian
authors: T
authors: Liu
authors: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287-5401, USA.
authors: Kenneth L
authors: KL
authors: Roland
authors: College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, 130118 Changchun, China.
authors: Yanlong
authors: Y
authors: Jiang
authors: Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, 611130 Chengdu, China; Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287-5401, USA. Electronic address: kongqiki@163.com.
authors: Qingke
authors: Q
authors: Kong
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D056738:Cross Protection; D004195:Disease Models, Animal; D000067128:Extracellular Vesicles / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000276:immunology* / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008807:Mice, Inbred BALB C; D009154:Mutation; D012480:Salmonella Infections / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D012486:Salmonella typhimurium / Q000737:chemistry* / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D022562:Salmonella Vaccines
keywords: Cross-protection; Lipopolysaccharide (LPS); Mouse model; Outer membrane vesicles (OMVs); Truncated LPS