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

Thomas D. Norton, Takuya Tada, Rebecca Leibowitz, Verena van der Heide, Dirk Homann, Nathaniel R. Landau

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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 cluster of differentiation 8 (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 (LCMV) model. Bone marrow-derived dendritic cells from SAMHD1 knockout mice were transduced with a lentiviral vector expressing the GP33 major-histocompatibility-complex (MHC)-class-I-restricted peptide epitope and CD40 ligand (CD40L) and injected into wild-type mice. The mice were highly protected against acute and chronic variant CL-13 LCMVs, 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; is applicable to the treatment of disease, including AIDS and cancer; and supports the utility of Vpx-containing vectors.

Original languageEnglish
Pages (from-to)1795-1805
Number of pages11
JournalMolecular Therapy
Issue number8
StatePublished - 5 Aug 2020


  • AIDS
  • CD8
  • LCMV
  • SAMHD1
  • Vpx
  • cancer
  • dendritic cell
  • lentiviral vector
  • vaccine


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