| Research Abstract |
The development of effective vaccine strategies for intracellular pathogens is one of major frontiers of current medical research. As dendritic cells (DCs) are the most potent antigen-presenting cells that initiate the primary immune response, they may provide an essential component of protective immunity against intracellular pathogens. In the present study, we attempted to develop genetically modified DC-based vaccine against Listeria monocytogenes (Lm), a facultative intracellular pathogen. Further, we determined the efficacy of the gene modified DC vaccine and also compared it with that of DNA vaccine. Murine bone marrow-derived DCs were retrovirally transduced with cDNA encoding lysteriolysin O (LLO) 91-99, a hemolysin produced by Lm, that is a H-2K^d-restricted target immunodominant epitope of antilisterial immunity. Naive BALB/c mice were immunized by intravenous injection of the transduced DCs. For DNA immunizaton, plasmid encoding LLO 91-99 was subcutaneouly injected using a gene gun. We found that specifically designed DC vaccine to express LLO 91-99 could effectively generate peptide-specific CD8+ T cells exhibiting strong cytotoxic activity and IFN-γ production, leading to induction of potent protective immunity against Lm. Furthermore, the DC-based vaccine was more effective than the DNA vaccine at eliciting anti-listerial immunity. These data suggest that gene modified DC vaccine expressing a single immunodominant epitope is useful for intracellular pathogen infection and may be superior to DNA vaccine, providing an alternative strategy for vaccine design against intracellular pathogens.
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