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In this study, we compare the in vivo efficiencies of activation of antigen-specific CD8 and CD4 T cells when the antigen is secreted by<jats:italic>L. monocytogenes<\/jats:italic>or when antigen-encoding plasmid DNA or mRNA is released by self-destructing strains of<jats:italic>L. monocytogenes<\/jats:italic>. Infection of mice with self-destructing<jats:italic>L. monocytogenes<\/jats:italic>carriers delivering mRNA that encodes a nonsecreted form of ovalbumin (OVA) resulted in a significant OVA-specific CD8 T-cell response. In contrast, infection with<jats:italic>L. monocytogenes<\/jats:italic>delivering OVA-encoding DNA failed to generate specific T cells. Secretion of OVA by the carrier bacteria yielded the strongest immune response involving OVA-specific CD8 and CD4 T cells. In addition, we investigated the antigen delivery capacity of a self-destructing, virulence-attenuated<jats:italic>L. monocytogenes aroA<\/jats:italic>\/<jats:italic>B<\/jats:italic>mutant. In contrast to the wild-type strain, this mutant exhibited only marginal liver toxicity when high doses (5 \u00d7 10<jats:sup>7<\/jats:sup>CFU per animal administered intravenously) were used, and it was also able to deliver sufficient amounts of secreted OVA into mice. Therefore, the results presented here could lay the groundwork for a rational combination of<jats:italic>L. monocytogenes<\/jats:italic>as an attenuated carrier for the delivery of protein and nucleic acid vaccines in novel vaccination strategies.<\/jats:p>","DOI":"10.1128\/iai.00112-06","type":"journal-article","created":{"date-parts":[[2006,6,21]],"date-time":"2006-06-21T23:10:29Z","timestamp":1150931429000},"page":"3946-3957","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Comparison of Different Live Vaccine Strategies In Vivo for Delivery of Protein Antigen or Antigen-Encoding DNA and mRNA by Virulence-Attenuated<i>Listeria monocytogenes<\/i>"],"prefix":"10.1128","volume":"74","author":[{"given":"Daniela I. 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