In Vitro and in Vivo Stability of Plasmids in Attenuated Salmonella enterica serovar typhimurium Used as a Carrier of DNA Vaccine is Associated with its Replication Origin

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The ability of live attenuated Salmonella enterica serovar typhimurium (S. typhimurium) as a carrier of DNA vaccine was evaluated using model plasmid encoding beta-galactosidase (β-Gal) and BALB/c mice. We constructed pBRCMVβ, β-Gal expression apparatus having a replication origin from low copy pBR322. Comparison of the plasmid stability showed that pBRCMVβ remained stable in Salmonella even after oral administration, while pUC-based pCMVβ tended to be lost quickly. However, titers for β-Gal specific IgG in sera did not significantly increase in mice orally administered S. typhimurium harboring pBRCMVβ. These data suggest that the stability of plasmid in S. typhimurium is associated with its replication origin. Further studies are required to scientifically establish this methodology.