Lentiviral Vector-based Dendritic Cell Vaccine Synergizes with Checkpoint Blockade to Clear Chronic Viral Infection

Abstract Dendritic cell vaccines are a promising strategy for the treatment of cancer and infectious diseases but have met with mixed success. We report on a lentiviral vector-based dendritic cell vaccine strategy that generates a CD8 T cell response that is much stronger than that achieved by standard peptide-pulsing approaches. The strategy was tested in the mouse lymphocytic choriomeningitis virus model. Bone marrow-derived dendritic cells from SAMHD1 knock-out mice were transduced with a lentiviral vector expressing the gp33 MHC class I-restricted peptide epitope and CD40L and injected into wild-type mice. The mice were highly protected against the Armstrong and chronic variant CL-13 viruses, resulting in a 100-fold greater decrease than that achieved with peptide epitope-pulsed dendritic cells. Inclusion of an MHC class II-restricted epitope in the lentiviral vector further increased the CD8 T cell response and resulted in antigen-specific CD8 T cells that exhibited a phenotype associated with functional cytotoxic T cells. The vaccination synergized with checkpoint blockade to reduce the viral load of mice chronically infected with CL-13 to an undetectable level. The strategy improves upon current dendritic cell vaccine strategies and is applicable to the treatment of disease including AIDS and cancer and supports the utility of Vpx-containing vectors.