{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T02:46:44Z","timestamp":1768272404359,"version":"3.49.0"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Stibitz lab fund"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We have been exploring the use of the live attenuated\n            <jats:named-content content-type=\"genus-species\">Salmonella enterica<\/jats:named-content>\n            serovar Typhi Ty21a vaccine strain as a versatile oral vaccine vector for the expression and delivery of multiple foreign antigens, including\n            <jats:named-content content-type=\"genus-species\">Shigella<\/jats:named-content>\n            O-antigens. In this study, we separately cloned genes necessary for the biosynthesis of the\n            <jats:named-content content-type=\"genus-species\">Shigella flexneri<\/jats:named-content>\n            serotype 2a and 3a O-antigens, which have been shown to provide broad cross-protection to multiple disease-predominant\n            <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n            serotypes. The cloned\n            <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n            2a\n            <jats:italic>rfb<\/jats:italic>\n            operon, along with\n            <jats:italic>bgt<\/jats:italic>\n            and\n            <jats:italic>gtrII<\/jats:italic>\n            , contained on the SfII bacteriophage, was sufficient in Ty21a to express the heterologous\n            <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n            2a O-antigen containing the 3,4 antigenic determinants. Further, this\n            <jats:italic>rfb<\/jats:italic>\n            operon, along with\n            <jats:italic>gtrA<\/jats:italic>\n            ,\n            <jats:italic>gtrB<\/jats:italic>\n            , and\n            <jats:italic>gtrX<\/jats:italic>\n            contained on the Sfx bacteriophage and\n            <jats:italic>oac<\/jats:italic>\n            contained on the Sf6 bacteriophage, was sufficient to express\n            <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n            3a O-antigen containing the 6, 7, and 8 antigenic determinants. Ty21a, with these plasmid-carried or chromosomally inserted genes, demonstrated simultaneous and stable expression of homologous\n            <jats:italic>S<\/jats:italic>\n            . Typhi O-antigen plus the heterologous\n            <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n            O-antigen. Candidate Ty21a vaccine strains expressing heterologous\n            <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n            2a or 3a lipopolysaccharide (LPS) elicited significant serum antibody responses against both homologous\n            <jats:italic>S<\/jats:italic>\n            . Typhi and heterologous\n            <jats:named-content content-type=\"genus-species\">Shigella<\/jats:named-content>\n            LPS and protected mice against virulent\n            <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n            2a or 3a challenges. These new\n            <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n            2a and 3a O-antigen-expressing Ty21a vaccine strains, together with our previously constructed Ty21a strains expressing\n            <jats:named-content content-type=\"genus-species\">Shigella sonnei<\/jats:named-content>\n            or\n            <jats:named-content content-type=\"genus-species\">Shigella dysenteriae<\/jats:named-content>\n            1 O-antigens, have the potential to be used together for simultaneous protection against the predominant causes of shigellosis worldwide as well as against typhoid fever.\n          <\/jats:p>","DOI":"10.1128\/cvi.00181-17","type":"journal-article","created":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T15:25:18Z","timestamp":1508340318000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Stable Chromosomal Expression of Shigella flexneri 2a and 3a O-Antigens in the Live Salmonella Oral Vaccine Vector Ty21a"],"prefix":"10.1128","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4954-2487","authenticated-orcid":false,"given":"Madushini N.","family":"Dharmasena","sequence":"first","affiliation":[{"name":"Laboratory of Mucosal Pathogens and Cellular Immunology, U.S. FDA-Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Osorio","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Pathogens and Cellular Immunology, U.S. FDA-Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyo","family":"Takeda","sequence":"additional","affiliation":[{"name":"Microscopy and Imaging Core Facility, U.S. FDA-Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Stibitz","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Pathogens and Cellular Immunology, U.S. FDA-Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis J.","family":"Kopecko","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Pathogens and Cellular Immunology, U.S. FDA-Center for Biologics Evaluation and Research, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Harrison's principles of internal medicine","author":"Keusch GT","year":"2005","unstructured":"Keusch GT KopeckoDJ. 2005. 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