FORGEN

RESEARCH NETWORK FOR FUNDAMENTAL GENETIC TECHNOLOGY

FORGEN II IS1 Development of newly designed recombinant live attenuated bacterial vaccine strains. Presentation of heterologous antigens by the plasmid-encoded type III secretion - translocation system of Yersinia enterocolitica

Throughout the world, bacterial, viral and parasitic diseases are still a major plague of mankind. The overall objective of the project is to develop more effective vaccines to fight infectious diseases. Many pathogens are transmitted to humankind by food from domestic cattle. Thus, vaccines designed in this project should be useful not only in immunizing human populations but also in the eradication of many human pathogens in animal reservoirs. Enteropathogenic Yersinia enterocolitica strains are promising candidates for the development of safe and effective live oral carrier vaccines for these purposes, because they colonize a wide range of mammalians and birds. Recently, we have genetically engineered Y. enterocolitica strains that cause a subclinical course of infection but retain their immunogenic properties to induce humoral and cellular immune responses. Conatct of Yersinia with host cells results in activation of a type III secretion- / translocation system that delivers a set of bacterial effector proteins into the environment or the host-cell cytosol. In this study, we will investigate the potential of this apparatus to deliver a model antigen of Listeria monocytogenes into different cellular and subcellular compartments of eukaryotic cells, thus stimulating different branches of the immune system against this antigen. The type III protein secretion-/ translocation system will expand the efficient use of Yersinia as a carrier of heterologous antigens to vaccinate against various infectious diseases.