Dendritic cells (DCs) are one of the key antigen presenting cells from the immune system to mount effective immune responses against pathogens and tumours. Several approaches for clinical trials involving this cell type are currently under study, including cellular vaccination using DCs loaded with both pathogen and tumour antigens.
However, these procedures, although providing promising results, are nowadays expensive and difficult to standarized. Therefore, this project will employ a rational design approach to the development of new vaccine vectors, by engineering lentivirus vectors specifically targeted to dendritic cells (DCs).
For this purpose, single chain antibodies (scFvs) specific for dendritic cells will be constructed from a phage display library. DC-specific scFvs will be fused to the MLV-A envelope protein through a blocking peptide followed by a matrix metalloprotease (MMP) recognition sequence. Lentivirus vectors based on defective HIV-1 genomes will be produced from stable packaging cell lines expressing DC-targeted chimeric scFv-MLV envelopes.
Transduction specificity and efficiency will be assayed both in cell cultures and in vivo. Antigens of interests will be expressed alone or co-expressed with DC-activating molecules, and immune responses against these antigens will be measured.
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