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Brief description/objective

Coronaviruses spread via mucosal surfaces and can infect dendritic cells. These features and their exceptional transcription strategy make them extremely promising candidate vaccine vectors to overcome known problems of current HIV vaccine approaches. The National Institutes of Health, Bethesda, USA, have granted to Partner 1 support to pursue this research line in the murine coronavirus system because of its innovation potential and since US researchers have not - yet - started to work in this direction. The European perspective of this project is thus to further promote this specific research line in Europe in order to pave the way for the generation of coronavirus-based HIV vaccines in humans. The AIDS-CoVAC consortium aims to generate a novel coronavirus-based HIV vaccine vector that is optimized for host entry by targeting professional antigen-presenting cells, namely dendritic cells (DCs). Recombinant coronavirus vectors in the context of a simian model could serve as a paradigm for the development and evaluation of coronavirus-based HIV vaccines.
The consortium consists of three scientific partners with well-matched, complementary, expertise and resources covering (i) the knowledge on coronavirus biology, reverse genetics and vector construction, (ii) an ample expertise on DC-based vaccination in murine models and human clinical trials, (iii) state-of-the-art technology to assess vector-DC interactions and, (iv) animal facilities and comprehensive experience for the evaluation of candidate AIDS vaccines in pre-clinical studies in monkeys. The collaborative and complementary research is divided into two scientific Work Packages. WP1 (Vector Generation and Optimization) involves the determination of the best suitable coronavirus spike protein for optimal vector entry into simian DCs and the analysis of vector-DC interactions by expression profiling, gene-clustering and advanced data mining. WP2 (Vector Evaluation) will assess the efficacy of vector-mediated gene transfer into simian DCs in vitro and the efficacy of this vaccination approach in vivo.