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VA-4 Genome-based vaccine strategies against HIV

Despite of excessive financial and scientific efforts, there is still no control of the HIV pandemic. Up to date, the development of effective vaccines failed mainly due to the complex biology and pathogenisis of the virus (e.g. drift and shift or loss of T helper cells). Over the last years, we developed HIV candidate vaccines which are currently evaluated in phase 1 clinical trials. Despite of initial promising results, the efficacy of this candidate vaccines still has to be increased. The aim of this project is to improve the maturation and activation of Dendritic cells (DC) resulting in a more effective presentation of relevant antigenic epitopes. Therefore, the existing candidate vaccine will be modified and tested in form of various delivery formats comprising virus like particles (VLP), naked plasmid DNA and a viral vector (EHV). Using transcriptome and proteome analyses the influence of facilitated uptake (baculoviral gp64 fusion protein) and adjuvation (mCD40ligand) on DC maturation and activation will be evaluated. The relevance of the resulting DC phenotypes for the differentiation of specific T-cells (ex vivo using PBMCs from HIV infected individuals) as well as the induction of specific cellular immune responses (in vivo in a Balb/c mouse model) will be assessed.


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