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Directly injected lentiviral vector–based T cell vaccine protects mice against acute and chronic viral infection
Takuya Tada, … , Rebecca Leibowitz, Nathaniel R. Landau
Takuya Tada, … , Rebecca Leibowitz, Nathaniel R. Landau
Published August 16, 2022
Citation Information: JCI Insight. 2022;7(18):e161598. https://doi.org/10.1172/jci.insight.161598.
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Research Article Immunology Vaccines

Directly injected lentiviral vector–based T cell vaccine protects mice against acute and chronic viral infection

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Abstract

Lentiviral vector–based dendritic cell vaccines induce protective T cell responses against viral infection and cancer in animal models. In this study, we tested whether preventative and therapeutic vaccination could be achieved by direct injection of antigen-expressing lentiviral vector, obviating the need for ex vivo transduction of dendritic cells. Injected lentiviral vector preferentially transduced splenic dendritic cells and resulted in long-term expression. Injection of a lentiviral vector encoding an MHC class I–restricted T cell epitope of lymphocytic choriomeningitis virus (LCMV) and CD40 ligand induced an antigen-specific cytolytic CD8+ T lymphocyte response that protected the mice from infection. The injection of chronically infected mice with a lentiviral vector encoding LCMV MHC class I and II T cell epitopes and a soluble programmed cell death 1 microbody rapidly cleared the virus. Vaccination by direct injection of lentiviral vector was more effective in sterile alpha motif and HD-domain containing protein 1–knockout (SAMHD1-knockout) mice, suggesting that lentiviral vectors containing Vpx, a lentiviral protein that increases the efficiency of dendritic cell transduction by inducing the degradation of SAMHD1, would be an effective strategy for the treatment of chronic disease in humans.

Authors

Takuya Tada, Thomas D. Norton, Rebecca Leibowitz, Nathaniel R. Landau

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Figure 1

Direct lentiviral vector injection extends the in vivo half-life of transduced cells.

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Direct lentiviral vector injection extends the in vivo half-life of tran...
(A) Diagram of the GFP/luciferase lentiviral vector GFP-NLuc (left). Wild-type and SAMHD1-knockout (KO) mice were injected i.p. with 1 × 107 infectious units (IU) of VSV-G–pseudotyped GFP-NLuc virus and imaged over time on an in vivo imaging systems (IVIS) imager as diagrammed (right). (B) Wild-type and SAMHD1-KO mice were injected with GFP/luciferase lentiviral vector and imaged at 1, 3, and 7 days postinjection (left). The image is pseudocolored according to luciferase signal intensity as shown on the bar at the right with colors corresponding to photons/s/mm2. Luciferase activity on day 7 (n = 6) was quantified by IVIS (right). Statistical significance was determined by 2-tailed, unpaired t test. Confidence intervals are shown as the mean ± SD. (****P ≤ 0.0001.) (C) SAMHD1-KO mice (n = 3) were injected with GFP-NLuc vector–transduced BMDCs (1 × 106 cells) or injected i.p. with GFP-NLuc virus (2 × 107 IU) and imaged on the indicated days. Luciferase activity was quantified as shown below.

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