title: Multiple antigens of Yersinia pestis delivered by live recombinant attenuated Salmonella vaccine strains elicit protective immunity against plague.
abstract: Based on our improved novel Salmonella vaccine delivery platform, we optimized the recombinant attenuated Salmonella typhimurium vaccine (RASV) χ12094 to deliver multiple Yersinia pestis antigens. These included LcrV196 (amino acids, 131-326), Psn encoded on pYA5383 and F1 encoded in the chromosome, their synthesis did not cause adverse effects on bacterial growth. Oral immunization with χ12094(pYA5383) simultaneously stimulated high antibody titers to LcrV, Psn and F1 in mice and presented complete protection against both subcutaneous (s.c.) and intranasal (i.n.) challenges with high lethal doses of Y. pestis CO92. Moreover, no deaths or other disease symptoms were observed in SCID mice orally immunized with χ12094(pYA5383) over a 60-day period. Therefore, the trivalent S. typhimurium-based live vaccine shows promise for a next-generation plague vaccine.
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.
authors.forename: Hetal
authors.initials: H
authors.lastname: Patel
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; School of Life Sciences, Arizona State University, Tempe, AZ, USA. Electronic address: rcurtiss@ufl.edu.
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D010930:Plague / Q000276:immunology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000276:immunology; D022562:Salmonella Vaccines / Q000235:genetics / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D015010:Yersinia pestis / Q000737:chemistry* / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic
keywords: F1 and Psn; LcrV; Plague; Recombinant Salmonella vaccine; Trivalent vaccine