Charakterisierung zellulärer Immunantworten von mit SIV immunisierten und infizierten Makaken

The infection with HIV and the resulting AIDS-disease are a global challenge for mankind. The infection of macaques with simian immunodeficiency virus (SIV) is the most important animal model for the development of a vaccine against this viral infection and for studies of pathogenesis in preclinical studies.In this thesis three prime-boost immunization regimes, varying in vector combinations and application route, were analyzed for their immunogenicity and efficiency against SIV-infection in this animal model. One particular focus was on the comparison between the cell- and cytokine-discriminating ICS-technology and the commonly used ELISPOT-technology for the detection of virus-specific immune responses. Furthermore, different blood T-cell populations and their variations after SIV-exposure were characterized with polychromatic flow cytometry. None of the three immunization regimes protected from SIV-infection, but the vaccinees had tenfold lower viral loads and better conserved their memory T-cells during the acute phase of infection compared to control animals. The direct comparison of ELISPOT- and ICS-technology in the second and third experiment displayed an increased secretion of IFNγ by virus-specific T-lymphocytes compared to control animals after infection. In addition, polyfunctional T-lymphocytes, secreting multiple cytokines simultaneously, could be detected in vaccinees of the third experiment after SIV-infection. In chronically SIV-infected animals, controlling viral replication for more than 70 weeks, virus-specific proliferating and polyfunctional T-cells were observed, whereas these cells were absent in animals with high viral loads.The results of this thesis allow us to characterize cellular immune responses in future animal studies of prophylaxis and pathogenesis in a more sophisticated way and analyze for potential immune correlates.