{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T01:32:44Z","timestamp":1792373564126,"version":"4.4.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T00:00:00Z","timestamp":1306886400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\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 Typhi, the agent of typhoid fever in humans, expresses the surface Vi polysaccharide antigen that contributes to virulence. However, Vi expression can also be detrimental to some key steps of\n            <jats:italic>S.<\/jats:italic>\n            Typhi infectivity, for example, invasion, and Vi is the target of protective immune responses. We used a strain of\n            <jats:italic>S.<\/jats:italic>\n            Typhimurium carrying the whole\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Salmonella<\/jats:named-content>\n            pathogenicity island 7 (SPI-7) to monitor\n            <jats:italic>in vivo<\/jats:italic>\n            Vi expression within phagocytic cells of mice at different times after systemic infection. We also tested whether it is possible to modulate Vi expression via the use of\n            <jats:italic>in vivo<\/jats:italic>\n            -inducible promoters and whether this would trigger anti-Vi antibodies through the use of Vi-expressing live bacteria. Our results show that Vi expression in the liver and spleen is downregulated with the progression of infection and that the Vi-negative population of bacteria becomes prevalent by day 4 postinfection. Furthermore, we showed that replacing the natural\n            <jats:italic>tviA<\/jats:italic>\n            promoter with the promoter of the SPI-2 gene\n            <jats:italic>ssaG<\/jats:italic>\n            resulted in sustained Vi expression in the tissues. Intravenous or oral infection of mice with a strain of\n            <jats:italic>S.<\/jats:italic>\n            Typhimurium expressing Vi under the control of the\n            <jats:italic>ssaG<\/jats:italic>\n            promoter triggered detectable levels of all IgG subclasses specific for Vi. Our work highlights that Vi is downregulated\n            <jats:italic>in vivo<\/jats:italic>\n            and provides proof of principle that it is possible to generate a live attenuated vaccine that induces Vi-specific antibodies after single oral administration.\n          <\/jats:p>","DOI":"10.1128\/iai.01265-10","type":"journal-article","created":{"date-parts":[[2011,3,15]],"date-time":"2011-03-15T20:28:48Z","timestamp":1300220928000},"page":"2481-2488","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["<i>In Vivo<\/i>\n            Regulation of the Vi Antigen in Salmonella and Induction of Immune Responses with an\n            <i>In Vivo<\/i>\n            -Inducible Promoter"],"prefix":"10.1128","volume":"79","author":[{"given":"Carole","family":"Janis","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevelyan J.","family":"McKinley","sequence":"additional","affiliation":[{"name":"Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona J. 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