Einsatz von dendritischen Zellen zur Impfung gegen Infektionskrankheiten
Projektleitung an der Universität Würzburg:
Beteiligte Wissenschaftlerinnen und Wissenschaftler:
The exquisite capacity of dendritic cells (DC) to sample microbial antigens, to respond to pathogen-derived signals and to stimulate primary T-cell responses provides the basis to use DC as an adjuvant for immunoprophylaxis and immunotherapy of infectious diseases. The studies in our laboratory demonstrated that DC loaded ex vivo with Leishmania major antigen mediate protection against infection with this protozoan parasite. The induction of protective immunity by DC-based vaccination involves the following mechanisms: 1. a shift in the cytokine profile from a T helper (Th) type 2 towards a Th1 response, 2. the production of interleukin 12 (IL-12) by DC in response to pulsing with L. major antigen, since antigen-loaded DC from IL-12-deficient mice are not able to mediate protection against the disease, and 3. the generation of long-lasting immunity, i.e. mice are still protected after considerable intervals (at least 6 weeks) between vaccination and infection and are resistant to a re-challenge with the parasites. In order to develop a DC-based vaccination strategy with molecularly defined components, we tested DC pulsed with recombinant Leishmania antigens. It was shown that DC loaded with a cocktail of defined antigens conferred high levels of protection. These results indicate that vaccination with DC carrying recombinant proteins or peptides may represent a novel approach for effective prophylactic and therapeutic immune interventions against infectious diseases.
Laufzeit: von 01.2001 bis 12.2004
DFG ,Genehmigungsdatum: 27.09.2000
Dendritic cells as adjuvant for immunization against infections