FORGEN

RESEARCH NETWORK FOR FUNDAMENTAL GENETIC TECHNOLOGY

FORGEN II IS3 Develpment and production of recombinant live vaccines based on a new Escherichia coli carrier system

Aim of the Project:

Development of new live vaccines consisting of the benevolent Escherichia coli strain DSM6601 and inactivated virulence genes of pathogenic bacteria. The resulting vaccines will be produced by our cooperation partner "Ardeypharm" GmbH.

The Project: Certain E. coli strains, pathogenic for humans, colonize farm animals without causing symptoms. These include enterohemorrhagic E. coli (EHEC) causing sometimes fatal disease also in Germany and enterotoxigenic E. coli responsible for diarrhea in travellers and children in third world countries. Both E. coli groups express adhesins and toxins, which constitute main virulence factors. The responsible genes will be molecularly cloned and mutagenized in order to loose virulence capacitiy but retain immunogenicity. The mutated genes will be expressed in E. coli strain DSM6601. The introduction of genes encoding an invasion system and/or the Listeria monocytogenes hemolysin will allow the vaccine strains to deliver the antigens into endosomes and/or the cytoplasm of host cells. This targeted delivery allows the induction of defined immune responses. Vaccination with the recombinant DSM6601 strains of e.g. cattle will block colonization of these animals by the corresponding bacterial pathogens. Additionally, the Mip antigen from Legionella pneumophila and Chlamydia will also be introduced into DSM6601 to generate vaccines against these intracellular pathogens. This project will not only produce new vaccines but will help to develop new strategies for vaccine designe.