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We have constructed attenuated\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Salmonella enterica<\/jats:named-content>\n            serovar Typhimurium and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Salmonella enterica<\/jats:named-content>\n            serovar Enteritidis strains that can serve as live oral vaccines and as \u201creagent strains\u201d for subunit vaccine production in a safe and economical manner. Prototype attenuated vaccine strains CVD 1921 and CVD 1941, derived from the invasive wild-type strains\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. Typhimurium<\/jats:named-content>\n            I77 and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. Enteritidis<\/jats:named-content>\n            R11, respectively, were constructed by deleting\n            <jats:italic>guaBA<\/jats:italic>\n            , encoding guanine biosynthesis, and\n            <jats:italic>clpP<\/jats:italic>\n            , encoding a master protease regulator. The\n            <jats:italic>clpP<\/jats:italic>\n            mutation resulted in a hyperflagellation phenotype. An additional deletion in\n            <jats:italic>fliD<\/jats:italic>\n            yielded reagent strains CVD 1923 and CVD 1943, respectively, which export flagellin monomers. Oral 50% lethal dose (LD\n            <jats:sub>50<\/jats:sub>\n            ) analyses showed that the NTS vaccine strains were all highly attenuated in mice. Oral immunization with CVD 1921 or CVD 1923 protected mice against lethal challenge with wild-type\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. Typhimurium<\/jats:named-content>\n            I77. Immunization with CVD 1941 but not CVD 1943 protected mice against lethal infection with\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. Enteritidis<\/jats:named-content>\n            R11. Immune responses induced by these strains included high levels of serum IgG anti-lipopolysaccharide (LPS) and anti-flagellum antibodies, with titers increasing progressively during the immunization schedule. Since\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. Typhimurium<\/jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. Enteritidis<\/jats:named-content>\n            are the most common NTS serovars associated with invasive disease, these findings can pave the way for development of a highly effective, broad-spectrum vaccine against invasive NTS.\n          <\/jats:p>","DOI":"10.1128\/iai.05278-11","type":"journal-article","created":{"date-parts":[[2011,8,2]],"date-time":"2011-08-02T02:57:50Z","timestamp":1312253870000},"page":"4175-4185","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":82,"title":["Engineering and Preclinical Evaluation of Attenuated Nontyphoidal Salmonella Strains Serving as Live Oral Vaccines and as Reagent Strains"],"prefix":"10.1128","volume":"79","author":[{"given":"Sharon M.","family":"Tennant","sequence":"first","affiliation":[{"name":"Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 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