Directly injected lentiviral vector–based T cell vaccine protects mice against acute and chronic viral infection
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 t...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-09-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.161598 |
| _version_ | 1827768012954927104 |
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| author | Takuya Tada Thomas D. Norton Rebecca Leibowitz Nathaniel R. Landau |
| author_facet | Takuya Tada Thomas D. Norton Rebecca Leibowitz Nathaniel R. Landau |
| author_sort | Takuya Tada |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T12:07:25Z |
| format | Article |
| id | doaj.art-3bfe8cd57d9b48468cad25ba2d2392ac |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:07:25Z |
| publishDate | 2022-09-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-3bfe8cd57d9b48468cad25ba2d2392ac2023-11-07T16:24:35ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-09-01718Directly injected lentiviral vector–based T cell vaccine protects mice against acute and chronic viral infectionTakuya TadaThomas D. NortonRebecca LeibowitzNathaniel R. LandauLentiviral 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.https://doi.org/10.1172/jci.insight.161598ImmunologyVaccines |
| spellingShingle | Takuya Tada Thomas D. Norton Rebecca Leibowitz Nathaniel R. Landau Directly injected lentiviral vector–based T cell vaccine protects mice against acute and chronic viral infection JCI Insight Immunology Vaccines |
| title | Directly injected lentiviral vector–based T cell vaccine protects mice against acute and chronic viral infection |
| title_full | Directly injected lentiviral vector–based T cell vaccine protects mice against acute and chronic viral infection |
| title_fullStr | Directly injected lentiviral vector–based T cell vaccine protects mice against acute and chronic viral infection |
| title_full_unstemmed | Directly injected lentiviral vector–based T cell vaccine protects mice against acute and chronic viral infection |
| title_short | Directly injected lentiviral vector–based T cell vaccine protects mice against acute and chronic viral infection |
| title_sort | directly injected lentiviral vector based t cell vaccine protects mice against acute and chronic viral infection |
| topic | Immunology Vaccines |
| url | https://doi.org/10.1172/jci.insight.161598 |
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