{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T01:31:05Z","timestamp":1792373465431,"version":"4.4.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2010,1,1]],"date-time":"2010-01-01T00:00:00Z","timestamp":1262304000000},"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":[[2010,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We hypothesized that adequately engineered attenuated\n            <jats:italic>Salmonella enterica<\/jats:italic>\n            serovar Typhi strains can serve as multivalent mucosal live vector vaccines to immunize against unrelated human pathogens. Toward this ultimate goal, we have developed a novel genetic stabilization system for antigen-expressing plasmids, engineered to encode the single-stranded binding protein (SSB), an essential protein involved in DNA metabolism which was deleted from the live vector chromosome. We utilized full-length protective antigen (PA83) of anthrax toxin from\n            <jats:italic>Bacillus anthracis<\/jats:italic>\n            as a foreign antigen and expressed PA83 as a fusion with the ClyA export protein, which allows export of ClyA-PA83 to the surface of\n            <jats:italic>S<\/jats:italic>\n            . Typhi live vectors. A series of SSB-encoding multicopy expression plasmids were introduced into reengineered\n            <jats:italic>S<\/jats:italic>\n            . Typhi strains previously tested in clinical trials, i.e., CVD 908-\n            <jats:italic>htrA<\/jats:italic>\n            and its less attenuated parent CVD 908. Immunogenicity was examined using a mouse model of intranasal immunization with live vector, followed by parenteral boosting with purified PA83. PA-specific antibody responses markedly improved as the copy number of the SSB-encoding plasmids decreased, and this effect was dramatically enhanced when the foreign antigen was delivered by the less attenuated live vector CVD 908\n            <jats:italic>ssb<\/jats:italic>\n            . These results suggest that antibody responses to antigens delivered by\n            <jats:italic>S<\/jats:italic>\n            . Typhi live vectors are inversely related to the metabolic burden imposed by expression of the foreign antigen and that these responses can be improved when antigens are expressed from low-copy-number plasmids and exported out of the cytoplasm of less attenuated live vectors.\n          <\/jats:p>","DOI":"10.1128\/iai.00916-09","type":"journal-article","created":{"date-parts":[[2009,11,3]],"date-time":"2009-11-03T03:04:21Z","timestamp":1257217461000},"page":"337-347","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["A New Generation of Stable, Nonantibiotic, Low-Copy-Number Plasmids Improves Immune Responses to Foreign Antigens in\n            <i>Salmonella enterica<\/i>\n            Serovar Typhi Live Vectors"],"prefix":"10.1128","volume":"78","author":[{"given":"James E.","family":"Galen","sequence":"first","affiliation":[{"name":"Center for Vaccine Development"},{"name":"Division of Geographic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development"},{"name":"Division of Geographic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magaly","family":"Chinchilla","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development"},{"name":"Division of Geographic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Vindurampulle","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development"},{"name":"Division of Geographic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey E.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development"},{"name":"Division of Geographic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haim","family":"Levy","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development"},{"name":"Division of Geographic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Blackwelder","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development"},{"name":"Division of Geographic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 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