title: Impact of plasmid stability on oral DNA delivery by Salmonella enterica serovar Typhimurium.
abstract: Live attenuated Salmonellae may overcome limitations with conventional methods of DNA immunisation. This study examined the impact of plasmid stability on oral DNA delivery by the attenuated Salmonella enterica serovar Typhimurium vaccine strain BRD509. A DNA vaccine cassette comprising the C fragment of tetanus toxin under control of the cytomegalovirus (CMV) promoter was ligated into plasmid pcDNA3, pUC18, pBBR122, pACYC184, pRSF1010/CAT, pBR322 and pAT153. In vitro and in vivo stability studies revealed that, with the exception of pcDNA3 and pUC18, the plasmids were retained by BRD509. However, pAT153 was the only plasmid to induce a tetanus toxoid-specific antibody response following oral delivery. Plasmid copy number was found to impact on plasmid stability and the induction of antigen-specific humoral responses.
authors.affiliation: Children's Vaccines Unit, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3001, Australia. michelleg@burnet.edu.au
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Gahan
authors.forename: Diane E
authors.initials: DE
authors.lastname: Webster
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wesselingh
authors.forename: Richard A
authors.initials: RA
authors.lastname: Strugnell
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity; D005260:Female; D008070:Lipopolysaccharides / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D022562:Salmonella Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D012485:Salmonella typhi / Q000276:immunology*; D013744:Tetanus Toxin / Q000235:genetics / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014436:Typhoid-Paratyphoid Vaccines / Q000235:genetics / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D022562:Salmonella Vaccines; D013744:Tetanus Toxin; D013745:Tetanus Toxoid; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA