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Effective vaccination using in vitro peptide-loaded heat-shock proteins (HSP), tumor-derived HSP and HSP fusion proteins has been shown in viral, parasite and tumor model systems. We demonstrate protective DNA vaccination using gp96-peptide fusion proteins against the intracellular bacterial pathogen Listeria monocytogenes in a mouse model. In contrast to previous studies using pathogen-derived HSP as vaccine vehicles, we used recombinant endogenous (Mus musculus) gp96 (GRP94) as a carrier for immunodominant listerial peptides. Analyses of the cellular immune response revealed profound epitope-specific IFN-gamma and cytotoxic T cell responses. Our findings suggest a predominantly MHC I-restricted T cell response to DNA vaccination with gp96 fusion proteins in the model employed. Most importantly, DNA vaccination induced protection against an otherwise lethal dose of L. monocytogenes.

DNA vaccination with gp96-peptide fusion proteins induces protection against an intracellular bacterial pathogen