Consequences of persistent antigen presentation following administration of HIV-1-derived lentiviral vectors

摘要: Lentiviral vectors (LVs) are promising tools for in vivo gene delivery, either to correct genetic defects or vaccination. Intravenous administration of LVs results stable transduction and expression the transgene antigen presenting cells (APCs) from spleen. Therefore, it was decided to investigate reasons for and consequences sustained these cells after systemic in vivo LVs. injection a LV encoding green fluorescent protein (GFP) resulted lymphocytes, macrophages all subsets of dendritic (DCs) spleen, detected 5 days later. In case of macrophages DCs, percentage transduced increased between and 30 injection. The dividing precursors contributes the persistence transgene-expressing as shown by BrdU incorporation. Expression ovalbumin (OVA) reduced number transgeneexpressing cells 30 days. However, remaining stimulated proliferation activation OVA-specific CD8+ T up 3 months LV administration, spite reduction status DCs over time. Mice also maintained cytolytic activity against OVA-pulsed targets following a single immunisation. conclusion, this thesis shows that LVs can transduce DCs and macrophages, leading persistent expression. These modified APCs are functional capable activating cells. be used for persistent modification APCs, opening opportunity their use in long-term immunomodulation.