title: Oral vaccination with salmonella simultaneously expressing Yersinia pestis F1 and V antigens protects against bubonic and pneumonic plague.
abstract: The gut provides a large area for immunization enabling the development of mucosal and systemic Ab responses. To test whether the protective Ags to Yersinia pestis can be orally delivered, the Y. pestis caf1 operon, encoding the F1-Ag and virulence Ag (V-Ag) were cloned into attenuated Salmonella vaccine vectors. F1-Ag expression was controlled under a promoter from the caf1 operon; two different promoters (P), PtetA in pV3, PphoP in pV4, as well as a chimera of the two in pV55 were tested. F1-Ag was amply expressed; the chimera in the pV55 showed the best V-Ag expression. Oral immunization with Salmonella-F1 elicited elevated secretory (S)-IgA and serum IgG titers, and Salmonella-V-Ag(pV55) elicited much greater S-IgA and serum IgG Ab titers than Salmonella-V-Ag(pV3) or Salmonella-V-Ag(pV4). Hence, a new Salmonella vaccine, Salmonella-(F1+V)Ags, made with a single plasmid containing the caf1 operon and the chimeric promoter for V-Ag allowed the simultaneous expression of F1 capsule and V-Ag. Salmonella-(F1+V)Ags elicited elevated Ab titers similar to their monotypic derivatives. For bubonic plague, mice dosed with Salmonella-(F1+V)Ags and Salmonella-F1-Ag showed similar efficacy (>83% survival) against approximately 1000 LD(50) Y. pestis. For pneumonic plague, immunized mice required immunity to both F1- and V-Ags because the mice vaccinated with Salmonella-(F1+V)Ags protected against 100 LD(50) Y. pestis. These results show that a single Salmonella vaccine can deliver both F1- and V-Ags to effect both systemic and mucosal immune protection against Y. pestis.
authors.affiliation: Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717, USA.
authors.forename: Xinghong
authors.initials: X
authors.lastname: Yang
authors.forename: B Joseph
authors.initials: BJ
authors.lastname: Hinnebusch
authors.forename: Theresa
authors.initials: T
authors.lastname: Trunkle
authors.forename: Catharine M
authors.initials: CM
authors.lastname: Bosio
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Suo
authors.forename: Mike
authors.initials: M
authors.lastname: Tighe
authors.forename: Ann
authors.initials: A
authors.lastname: Harmsen
authors.forename: Todd
authors.initials: T
authors.lastname: Becker
authors.forename: Kathryn
authors.initials: K
authors.lastname: Crist
authors.forename: Nancy
authors.initials: N
authors.lastname: Walters
authors.forename: Recep
authors.initials: R
authors.lastname: Avci
authors.forename: David W
authors.initials: DW
authors.lastname: Pascual
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D007125:Immunogenetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology; D010930:Plague / Q000276:immunology* / Q000517:prevention & control; D012475:Salmonella / Q000235:genetics / Q000276:immunology*; D012480:Salmonella Infections / Q000276:immunology* / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015996:Survival Rate; D015009:Yersinia Infections; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D000906:Antibodies; D000942:Antigens, Bacterial; D022562:Salmonella Vaccines