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

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.