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This is an antibiotic resistance-free maintenance system containing the<jats:italic>asdA<\/jats:italic>gene (essential for peptidoglycan synthesis) as a selectable marker to complement the lethal chromosomal \u0394<jats:italic>asdA<\/jats:italic>allele in live recombinant attenuated<jats:italic>Salmonella<\/jats:italic>vaccines (RASVs) such as<jats:italic>Salmonella enterica<\/jats:italic>serovar Typhimurium strain \u03c79447. pYA4534 harbors two origins of replication, pSC101 and pUC (low and high copy numbers, respectively). The pUC replication origin is controlled by a genetic switch formed by the operator\/promoter of the P22<jats:italic>cro<\/jats:italic>gene (O\/P<jats:sub>cro<\/jats:sub>) (P<jats:sub>R<\/jats:sub>), which is negatively regulated by an arabinose-inducible P22<jats:italic>c2<\/jats:italic>gene located on both the plasmid and the chromosome (<jats:italic>araC<\/jats:italic>P<jats:sub>BAD<\/jats:sub><jats:italic>c2<\/jats:italic>). The absence of arabinose, which is unavailable<jats:italic>in vivo<\/jats:italic>, triggers replication to a high-copy-number plasmid state. To validate these vector attributes, the<jats:italic>Yersinia pestis<\/jats:italic>virulence antigen LcrV was used to develop a vaccine against plague. An<jats:italic>lcrV<\/jats:italic>sequence encoding amino acids 131 to 326 (LcrV196) was optimized for expression in<jats:italic>Salmonella<\/jats:italic>, flanked with nucleotide sequences encoding the signal peptide (SS) and the carboxy-terminal domain (CT) of \u03b2-lactamase, and cloned into pYA4534 under the control of the P<jats:sub>trc<\/jats:sub>promoter to generate plasmid pYA4535. Our results indicate that the live<jats:italic>Salmonella<\/jats:italic>vaccine strain \u03c79447 harboring pYA4535 efficiently stimulated a mixed Th1\/Th2 immune response that protected mice against lethal challenge with<jats:italic>Y. pestis<\/jats:italic>strain CO92 introduced through either the intranasal or subcutaneous route.<\/jats:p>","DOI":"10.1128\/iai.00005-10","type":"journal-article","created":{"date-parts":[[2010,3,23]],"date-time":"2010-03-23T02:24:18Z","timestamp":1269311058000},"page":"2529-2543","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Fine-Tuning Synthesis of<i>Yersinia pestis<\/i>LcrV from Runaway-Like Replication Balanced-Lethal Plasmid in a<i>Salmonella enterica<\/i>Serovar Typhimurium Vaccine Induces Protection against a Lethal<i>Y. pestis<\/i>Challenge in Mice"],"prefix":"10.1128","volume":"78","author":[{"given":"Ascencio\u0301n","family":"Torres-Escobar","sequence":"first","affiliation":[{"name":"Center for Infectious Diseases and Vaccinology at Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona 85287-5401"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari\u0301a Dolores","family":"Jua\u0301rez-Rodri\u0301guez","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Vaccinology at Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona 85287-5401"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bronwyn M.","family":"Gunn","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Vaccinology at Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona 85287-5401"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine G.","family":"Branger","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Vaccinology at Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona 85287-5401"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven A.","family":"Tinge","sequence":"additional","affiliation":[{"name":"MEGAN Health, Inc., St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"Roy","family":"Curtiss","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases and Vaccinology at Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, Arizona 85287-5401"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr070036r"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.62.3.293-300.1951"},{"key":"e_1_3_2_4_2","first-page":"234","volume":"2","year":"1984","unstructured":"Bochner, B. 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