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To elucidate the relationship between organs within which vaccine organisms are found and the induction of specific serum immunoglobulin G (IgG) antibodies, we examined the in vivo distribution of serovar Typhi vaccine strain CVD 908-<jats:italic>htrA<\/jats:italic>following intranasal administration. Vaccine organisms were cultured from the nasal lymphoid tissue (NALT), lungs, and Peyer's patches 2 min after intranasal inoculation. Vaccine organisms persisted longer in NALT than in other organs. By decreasing the volume of intranasal inoculum containing 10<jats:sup>9<\/jats:sup>CFU (from a single 30- or 10-\u03bcl dose to four 2.5-\u03bcl doses given over the course of 1 h), we were able to significantly reduce the number of vaccine organisms isolated from the lungs (<jats:italic>P<\/jats:italic>&lt; 0.05) without reducing the number of vaccine organisms in NALT. Reducing the number of vaccine organisms in the lungs resulted in a significant decrease in the serum tetanus antitoxin response elicited by CVD 908-<jats:italic>htrA<\/jats:italic>expressing tetanus toxin fragment C under the control of the redox-responsive<jats:italic>nir15<\/jats:italic>promoter. In contrast, a similar construct expressing tetanus toxin fragment C under control of the constitutive<jats:italic>lpp<\/jats:italic>promoter stimulated a strong serum IgG tetanus antitoxin response with both inoculation regimens. The data suggest that following intranasal inoculation, NALT is a sufficient inductive site for elicitation of an immune response against both the live vector and heterologous antigen and, as occurs following oral inoculation of humans, attenuated serovar Typhi vaccine organisms elicit serum IgG responses.<\/jats:p>","DOI":"10.1128\/iai.68.1.205-213.2000","type":"journal-article","created":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T17:57:25Z","timestamp":1241200645000},"page":"205-213","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":67,"title":["In Vivo Characterization of the Murine Intranasal Model for Assessing the Immunogenicity of Attenuated<i>Salmonella enterica<\/i>Serovar Typhi Strains as Live Mucosal Vaccines and as Live Vectors"],"prefix":"10.1128","volume":"68","author":[{"given":"Thames E.","family":"Pickett","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, and Division of Infectious Diseases and Tropical Pediatrics, Department of Pediatrics,1 and"},{"name":"<!--label omitted: 2-->Department of Microbiology and Immunology,2 University of Maryland School of Medicine, Baltimore, Maryland 21201"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela F.","family":"Pasetti","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, and Division of Infectious Diseases and Tropical Pediatrics, Department of Pediatrics,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James E.","family":"Galen","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, and Division of Infectious Diseases and Tropical Pediatrics, Department of Pediatrics,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo B.","family":"Sztein","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, and Division of Infectious Diseases and Tropical Pediatrics, Department of Pediatrics,1 and"},{"name":"<!--label omitted: 2-->Department of Microbiology and Immunology,2 University of Maryland School of Medicine, Baltimore, Maryland 21201"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myron M.","family":"Levine","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, and Division of Infectious Diseases and Tropical Pediatrics, Department of Pediatrics,1 and"},{"name":"<!--label omitted: 2-->Department of Microbiology and Immunology,2 University of Maryland School of Medicine, Baltimore, Maryland 21201"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.10.4172-4181.1996"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.10.4.816-822.1974"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.139.5.1189"},{"key":"e_1_3_2_5_2","first-page":"888","article-title":"Use of the nirB promoter to direct the stable expression of heterologous antigens in Salmonella oral vaccine strains: development of a single-dose oral tetanus vaccine","volume":"10","author":"Chatfield S. 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