Oral immunization with HCV-NS3—transformed Salmonella: Induction of HCV-specific CTL in a transgenic mouse model

Abstract Background & Aims: The ability to induce cytotoxic T cells is considered an important feature of a candidate hepatitis C virus (HCV) vaccine. We used an oral immunization strategy with attenuated HCV-NS3–transformed Salmonella typhimurium to deliver DNA directly to the gut-associated lymphoid tissue. Methods: HLA-A2.1 transgenic mice were immunized once with transformed attenuated Salmonella . HCV-specific CD8 + T cells were analyzed in vitro as well as in vivo by challenge of mice with recombinant HCV-NS3 vaccinia virus. Results: Salmonella (10 8 colony-forming units; 20 μg plasmid DNA) induced cytotoxic and IFN-γ–producing CD8 + T cells specific for the immunodominant epitope NS3-1073 in 26 of 30 mice (86%) that persisted for at least 10 months. A second epitope (NS3-1169) was also recognized by cytotoxic and IFN-γ–producing T cells, whereas a third one (NS3-1406) stimulated IFN-γ production without cytotoxicity. The minimal amount of plasmid DNA required to induce CTLs was 2 ng. Upon challenge with recombinant HCV-NS3–expressing vaccinia virus, vaccinia titers were significantly lower in mice immunized with Salmonella -NS3 than in mice immunized with control Salmonella , demonstrating the in vivo function of CTLs. Conclusions: Oral immunization with attenuated Salmonella typhimurium as a carrier for HCV DNA induces long-lasting T-cell responses. GASTROENTEROLOGY 2001;121:1158-1166