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Then, we inserted the<jats:italic>asd<\/jats:italic>mutation into this construction to form \u03c710057 [\u0394<jats:italic>asd-206<\/jats:italic>\u0394<jats:italic>msbB868<\/jats:italic>::P<jats:sub>msbB<\/jats:sub><jats:italic>msbB<\/jats:italic><jats:sub>(EC)<\/jats:sub>\u0394P<jats:sub>crp21<\/jats:sub>::TT<jats:italic>araC<\/jats:italic>P<jats:sub>BAD<\/jats:sub><jats:italic>crp<\/jats:italic>] for use with a balanced-lethal Asd-positive (Asd<jats:sup>+<\/jats:sup>) plasmid to facilitate antigen synthesis. A hybrid protein composed of YopE (amino acids [aa]1 to 138) fused with full-length LcrV (YopE<jats:sub>Nt138<\/jats:sub>-LcrV) was synthesized in \u03c710057 harboring an Asd<jats:sup>+<\/jats:sup>plasmid (pYA5199,<jats:italic>yopE<jats:sub>Nt138<\/jats:sub>-lcrV<\/jats:italic>) and could be secreted through a type III secretion system (T3SS)<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. Animal studies indicated that mice orally immunized with \u03c710057(pYA5199) developed titers of IgG response to whole-cell lysates of<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>(YpL) and subunit LcrV similar to those seen with \u03c710057(pYA3332) (\u03c710057 plus an empty plasmid). However, only immunization of mice with \u03c710057(pYA5199) resulted in a significant secretory IgA response to LcrV. \u03c710057(pYA5199) induced a higher level of protection (80% survival) against intranasal (i.n.) challenge with \u223c240 median lethal doses (LD<jats:sub>50<\/jats:sub>) (2.4 \u00d7 10<jats:sup>4<\/jats:sup>CFU) of<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>KIM6+(pCD1Ap) than \u03c710057(pYA3332) (40% survival). Splenocytes from mice vaccinated with \u03c710057(pYA5199) produced significant levels of gamma interferon (IFN-\u03b3), tumor necrosis factor alpha (TNF-\u03b1), and interleukin-17 (IL-17) after restimulation with LcrV and YpL antigens. Our results suggest that it is possible to use an attenuated<jats:named-content content-type=\"genus-species\">Y. pseudotuberculosis<\/jats:named-content>strain delivering the LcrV antigen via the T3SS as a potential vaccine candidate against pneumonic plague.<\/jats:p>","DOI":"10.1128\/iai.02173-14","type":"journal-article","created":{"date-parts":[[2014,8,12]],"date-time":"2014-08-12T04:05:46Z","timestamp":1407816346000},"page":"4390-4404","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["LcrV Delivered via Type III Secretion System of Live Attenuated Yersinia pseudotuberculosis Enhances Immunogenicity against Pneumonic Plague"],"prefix":"10.1128","volume":"82","author":[{"given":"Wei","family":"Sun","sequence":"first","affiliation":[{"name":"Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Sanapala","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy C.","family":"Henderson","sequence":"additional","affiliation":[{"name":"The Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shandiin","family":"Sam","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Olinzock","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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