Achieving Protective Immunity Against Intracellular Bacterial Pathogens: A Study on the Efficiency of Gp96 as a Vaccine Carrier

Effective vaccination using in vitro peptide-loaded heat shock proteins, tumor-derived heat shock proteins, and heat shock-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 heat shock proteins 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-γ 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.