FORINGEN

RESEARCH NETWORK FOR INFECTOGENOMICS

I5 I5 - Application of new genetical high through-put methods for the optimisation of herpesviral live vaccines

Issues of future research:
A new approach based on state-of-the-art molecular biology methods will be applied for the development of a new generation of live vaccines. Until today live vaccines are gained by unspecific attenuation of pathogens - mainly by spontaneous mutation or passaging of the pathogen in cell culture. However, the genetic manifestation of the attenuation (which gene is affected') remains unclear. For the first time, our project intends to systematically investigate the role of specific herpesviral gene functions with regard to the importance for an effective live vaccine. Several already identified immunmodulatory and cell biologically relevant viral genes are potentially important candidates. Our group has developed new approaches for manipulation of the very large (up to 230 kbp) herpesviral genomes, which will be applied for the vaccine development. It is now possible to generate in high through-put a large number of virus mutants which lack individual genes. These mutants will first be investigated in cell culture and subsequently analysed in the mouse model with respect to their ability to initiate an efficient immune response and to cause only minor or no pathogenicity. Hereby, the composition of an improved herpesviral live vaccine can be determined gene by gene. Within the scope of this project we will paradigmatically investigate the murine Cytomegalovirus (MCMV) and subsequently transfer the new knowledge to the Marek Disease Virus for generation of a new live-vaccine against the Marek´s Disease.