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Third-party-funded project

Title:
Development of oral live vaccines with virulence-attenuated bacteria carrying novel vectors

Project management at the University of Würzburg:

• Prof. Dr. Werner Goebel ,Tel: 0931/8884401,Fax: 0931/8884402,Mail: goebel@biozentrum.uni-wuerzburg.de

Participating scientists:

• Dr. Sabine Pilgrim ,Tel: 0931/8884408,Fax: 0931/8884402,Mail: pilgrim@biozentrum.uni-wuerzburg.de
• Dipl.-Biol. Jochen Stritzker ,Tel: 0931/8884408,Fax: 0931/8884402,Mail: j-stritzker@biozentrum.uni-wuerzburg.de
• PD Dr. Ivaylo Gentschev
• Dr. med. Christoph Schoen ,Tel: 0931/8884408,Fax: 0931/8884402,Mail: cuschoen@biozentrum.uni-wuerzburg.de

Abstract:
The aim of this project is the development of new strategies for the production of vaccines using live virulence-attenuated bacteria. Protective protein antigens are either directly secreted into the phagosome or the cytosol of antigen-presenting cells such as macrophages and dendritic cells or plasmid DNA encoding such antigens is released into the cytosol of these cells were the respective genes are expressed. By variation of the carrier bacteria the immune response can be modified (either predominant Th1 or CTL responses) and by the introduction of suitable mutations into the carrier bacteria the biosafety of the live vaccines can be significantly improved.

Key words:
    Live vaccines

Projekt period: from 06.2002 to 05.2003

Funding institution:
DFG ,Granting date: 05.03.2001

Publications:

• Spreng, S, Dietrich, G., Goebel, W., Gentschev, I.. (1999). The Escherichia coli haemolysin secretion apparatus: a potential universal antigen delivery system in gram-negative bacterial vaccine carriers.. (monograph)
• Geginat, G., Nichterlein, T., Kretschmar, M., Schenk, S., Hof, H., Lalic-Mülthaler, M., Goebel, W., Bubert. (1999). Enhancement of the Listeria monocytogenes p60-specific CD4 and D8 T cell memory by nonpathogenic Listeria innocua. (monograph)
• Dietrich, G., Gentschev, I., Hess, J., Ulmer, J.B., Kaufmann, S.H., Goebel, W.. (1999). Delivery of DNA vaccines by attenuated intracellular bacteria.. (monograph)
• Catic, A., Dietrich, G., Gentschev, I., Goebel, W., Kaufmann, SH. and Hess, J.. (1999). Introduction of protein or DNA delivered via recombinant Salmonella typhimurium into the major histocompatibility complex class I presentation pathway of macrophages. (monograph)
• Kimmel, B., Bosserhoff, A., Frank, R., Gross, R., Goebel, W. and Beier, D.. (2000). Identification of immunodominant Antigens from Helicobacter pylori and evalution of their reactivities with sera from patients with different gastroduodenal pathologies.. (monograph)
• Dietrich, G., Spreng, S., Gentschev, I. and Goebel, W.. (2000). Bacterial systems for the delivery of eukaryotic antigen expression vector.. (monograph)
• Gentschev, I., Dietrich, G., Spreng, S., Kolb-Mäurer, A., Daniels, J., Hess, J., Kaufmann, S.H. and Goebel, W.. (2000). Delivery of protein antigens and DNA by virulence-attenuated strains of Salmonella typhimurium and Listeria monocytogenes.. (monograph)
• Rüssmann, H., Weissmüller, A., Geginat, G. Igwe E.I., Roggenkamp, A., Bubert, A., Goebel, W., Hof, H. and Heesemann. (2000). Yersinia enterocolitica-mediated translocation of defined fusion proteins to the cytosol of mammalian cells results in peptide-specific MHC classI-restriction antigen presentation.. (monograph)
• Kolb-Mäurer, A., Gentschev. I., Fries, H.W., Fiedler, F., Brocker, E.B., Kampgen, E. and Goebel, W.. (2000). Listeria monocytogenes-infected human dendritic cells: uptake and host cell response.. (monograph)
• Dietrich, G. and Goebel, W.. (2000). DNA vaccine delivery by attenuated intracellular bacteria.. (monograph)
• Spreng, S. , Gentschev, I.,Goebel, W., Mollenkopf, H, Eck, M., Müller-Hermelink H.K., and Schmausser, B.. (2000). Identification of immunogenic antigens of Helicobacter pylori via the Escherichia coli hemolysin secretion system (1).. (monograph)
• Spreng, S. , Gentschev, I.,Goebel, W., Mollenkopf, H, Eck, M., Müller-Hermelink H.K., and Schmausser, B.. (2000). Novel bacterial systems for the delivery of recombinant protein or DNA.. (monograph)
• Hess, J., Grode, L., Hellwig, J., Conradt, P., Gentschev, I., Goebel, W. , Ladel, C., Kaufmann, S.H.. (2000). Protein against murine tuberculosis by an attenuated revombinant Salmonella typhimurium vaccine strain that secretes the 30-kDa antigen of Miycobacterium bovis BCG.. (monograph)
• Dietrich, G. and Goebel, W.. (2000). DNA vaccine delivery by attenuated intracellular bacteria.. (monograph)
• Spreng, S, Gentschev, I, Goebel, W, Weidinger, G, ter Meulen, V, Niewiesk, S.. (2000). Salmonella vaccines secreting measles virus epitopes induce protective immune responses agains measles virus encephalitis.. (monograph)
• Hess, J., Grode, L, Gentschev, I., Fensterle, J., Dietrich, G., Goebel, W., Kaufmann ,S.H.. (2000). Secretion of different listeriolysin cognates by recombinant attenuated Salmonella typhimurium: superior efficacy of haemolytic over non-haemolytic constructs after oral vaccination.. (monograph)
• Russmann, H., Weissmuller, A., Geginat, G., Igwe, E.I., Roggenkamp, A., Bubert, A., Goebel, W., Hof, H., Heesemann. J.. (2000). Yersinia enterocolitica-mediated translocation of defined fusion proteins to the cytosol of mammalian cells results in peptide-specific MHC class I-restricted antigen presentation.. (monograph)
• Dietrich, G., Hess, J., Gentschev, I., Knapp, B., Kaufmann, S.H., Goebel, W.. (2001). From evil to good: a cytolysin in vaccine development.. (monograph)
• Gentschev, I., Dietrich, G., Spreng, S., Kolb-Maurer, A., Brinkmann, V., Grode, L., Hess, J., Kaufmann, S.H., Goebel, W.. (2001). Recombinant attenuated bacteria for the delivery of subunit vaccines.. (monograph)
• Dietrich, G., Kolb-Maurer, A., Spreng, S., Schartl, M., Goebel, W., Gentschev, I.. (2001). Gram-positive and Gram-negative bacteria as carrier systems for DNA vaccines.. (monograph)
• Geginat, G., Schenk, S., Skoberne, M., Goebel, W., Hof, H.. (2001). A novel approach of direct ex vivo epitope mapping identifies dominant and subdominant CD4 and CD8 T cell epitopes from Listeria monocytogenes.. (monograph)

Links:
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