FORGEN

RESEARCH NETWORK FOR FUNDAMENTAL GENETIC TECHNOLOGY

FORGEN II IS2 Safety and efficiency of recombinant bacterial live vaccines in immuno competent and immuno deficient mice.

The progress in molecular biology of pathogenic bacteria and advances in gene technology revealed the prerequisites for the development of novel vaccines. By means of life vaccines it should be possible to deliver components of pathogens to the immune system in order to induce strong and protective immunity. However, prior to administration of novel vaccines to man, both safety and efficacy need to be established. The current available life vaccines can, although very rarely, induce severe infection, particularly in immunodeficient patients. Recent studies suggest that several immunodeficiencies occur more frequent than previously believed. By means of transgenic mice, some of these immunodeficiencies can be studied, particularly their impact on vaccination. The aim of the project is to evaluate the degree of attenuation of recombinant Yersinia and Salmonella vaccine strains in both immunocompetent and immunodeficient mice. By this means, novel vaccine strains will be identified that induce efficient immune responses, but are nevertheless significantly attenuated. Several genetically engineered attenuated bacteria will be used for immunization in transgenic immunodeficient mice. Moreover, we will analyze how host factors modulate bacterial gene expression including expression of heterologous antigens. Finally, immune responses to and safety of life vaccines will be studied. The results of these investigations should reveal novel, molecular and immunologically well evaluated life vaccines. The project is part of an interactive complementary network including the groups of Prof. Heesemann (Munich) and Creatogen GmbH (Augsburg), a biotech company specialized on the development of novel bacterial life vaccines.