title: Oral administration of a recombinant attenuated Yersinia pseudotuberculosis strain elicits protective immunity against plague.
abstract: A Yersinia pseudotuberculosis PB1+ (Yptb PB1+) mutant strain combined with chromosome insertion of the caf1R-caf1A-caf1M-caf1 operon and deletions of yopJ and yopK, χ10068 [pYV-ω2 (ΔyopJ315 ΔyopK108) ΔlacZ044::caf1R-caf1M-caf1A-caf1] was constructed. Results indicated that gene insertion and deletion did not affect the growth rate of χ10068 compared to wild-type Yptb cultured at 26 °C. In addition, the F1 antigen in χ10068 was synthesized and secreted on the surface of bacteria at 37 °C (mammalian body temperature), not at ambient culture temperature (26 °C). Immunization with χ10068 primed antibody responses and specific T-cell responses to F1 and YpL (Y. pestis whole cell lysate). Oral immunization with a single dose of χ10068 provided 70% protection against a subcutaneous (s.c.) challenge with ∼ 2.6 × 10(5) LD50 of Y. pestis KIM6+ (pCD1Ap) (KIM6+Ap) and 90% protection against an intranasal (i.n.) challenge with ∼ 500 LD50 of KIM6+Ap in mice. Our results suggest that χ10068 can be used as an effective precursor to make a safe vaccine to prevent plague in humans and to eliminate plague circulation among humans and animals.
authors.affiliation: Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. Electronic address: wsun8@ufl.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Sanapala
authors.affiliation: Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Rahav
authors.affiliation: Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Life Sciences, Arizona State University, Tempe, AZ, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D051379:Mice; D016254:Mutagenesis, Insertional; D010930:Plague / Q000276:immunology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage / Q000276:immunology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D010931:Plague Vaccine; D014613:Vaccines, Attenuated; D037521:Virulence Factors; C086725:caf1 protein, Yersinia pestis
keywords: F1; Plague; Vaccine; Yersinia pseudotuberculosis