title: Outer membrane vesicles from flagellin-deficient Salmonella enterica serovar Typhimurium induce cross-reactive immunity and provide cross-protection against heterologous Salmonella challenge.
abstract: Outer membrane vesicles (OMVs) isolated from Salmonella Typhimurium are potentially useful for developing subunit vaccines because of high immunogenicity and protective efficacy. However, flagella might remain in OMV pellets following OMV purification, resulting in non-essential immune responses and counteraction of bacterial protective immune responses when developing a vaccine against infection of multiple serotypes Salmonella. In this study, a flagellin-deficient S. Typhimurium mutant was constructed. Lipopolysaccharide profiles, protein profiles and cryo-electron microscopy revealed that there were no significant differences between the wild-type and mutant OMVs, with the exception of a large amount of flagellin in the wild-type OMVs. Neither the wild-type OMVs nor the non-flagellin OMVs were toxic to macrophages. Mice immunized with the non-flagellin OMVs produced high concentrations of IgG. The non-flagellin OMVs elicited strong mucosal antibody responses in mice when administered via the intranasal route in addition to provoking higher cross-reactive immune responses against OMPs isolated from S. Choleraesuis and S. Enteritidis. Both intranasal and intraperitoneal immunization with the non-flagellin OMVs provided efficient protection against heterologous S. Choleraesuis and S. Enteritidis challenge. Our results indicate that the flagellin-deficient OMVs may represent a new vaccine platform that could be exploited to facilitate the production of a broadly protective vaccine.
authors.affiliation: Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, 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, Nanchang, 330006, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yi
authors.affiliation: Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Liang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX, 77030, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy/Health Sciences, Wayne State University, Detroit, MI, 48202, USA.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ, 85287-5401, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
authors.affiliation: Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.|Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ, 85287-5401, USA.
authors.forename: Qingke
authors.initials: Q
authors.lastname: Kong
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage* / Q000276:immunology; D056738:Cross Protection; D003429:Cross Reactions; D005408:Flagellin / Q000235:genetics*; D017353:Gene Deletion; D007114:Immunization; D007074:Immunoglobulin G / Q000378:metabolism; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000517:prevention & control*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D007074:Immunoglobulin G; D005408:Flagellin