Viral vectors for vaccination can be optimized by targeting vector entry to antigen-presenting cells (APCs). Here we describe lentiviral vectors (LVs) that are targeted to APC using a chimeric measles virus (MV) hemagglutinin (H). The MV H protein is mutated to prevent binding to MV receptors and incorporates a single-chain antibody that recognizes murine major histocompatibility complex class II (MHC II). This targeted LV is highly efficient in transduction of freshly isolated mouse B cells and dendritic cells. MHC II–positive cells in spleen are transduced after intravenous injection, and a robust immune response to an antigen transgene is generated.
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