title: DNA vaccination with gp96-peptide fusion proteins induces protection against an intracellular bacterial pathogen.
abstract: 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.
authors.affiliation: Max Planck Institute for Infection Biology, Schumannstrasse 21-22, 10117 Berlin, Germany.
authors.forename: Ulrike K
authors.initials: UK
authors.lastname: Rapp
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology; D006460:Hemolysin Proteins; D015151:Immunoblotting; D007371:Interferon-gamma / Q000378:metabolism; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control*; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology* / Q000627:therapeutic use
chemical_list: C078516:60 kDa protein, Listeria monocytogenes; D000951:Antigens, Neoplasm; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C052646:sarcoma glycoprotein gp96 rejection antigens; D007371:Interferon-gamma; C038705:hlyA protein, Listeria monocytogenes