1. Lentiviral Vector-Based Dendritic Cell Vaccine Suppresses HIV Replication in Humanized Mice
- Author
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Norton, Thomas D, Zhen, Anjie, Tada, Takuya, Kim, Jennifer, Kitchen, Scott, and Landau, Nathaniel R
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Prevention ,HIV/AIDS ,Infectious Diseases ,Vaccine Related ,Biotechnology ,Human Fetal Tissue ,Immunization ,Infection ,Good Health and Well Being ,AIDS Vaccines ,Animals ,CD40 Ligand ,CD8-Positive T-Lymphocytes ,Dendritic Cells ,Epitopes ,T-Lymphocyte ,Genetic Vectors ,HIV Infections ,HIV-1 ,Humans ,Lymphocyte Activation ,Mice ,Programmed Cell Death 1 Receptor ,T-Lymphocytes ,Cytotoxic ,Virus Replication ,HIV ,Vpx ,checkpoint inhibitor ,dendritic cell vaccine ,humanized mice ,lentiviral vector ,Biological Sciences ,Technology ,Medical and Health Sciences ,Genetics ,Clinical sciences ,Medical biotechnology - Abstract
HIV-1-infected individuals are treated with lifelong antiretroviral drugs to control the infection. A means to strengthen the antiviral T cell response might allow them to control viral loads without antiretroviral drugs. We report the development of a lentiviral vector-based dendritic cell (DC) vaccine in which HIV-1 antigen is co-expressed with CD40 ligand (CD40L) and a soluble, high-affinity programmed cell death 1 (PD-1) dimer. CD40L activates the DCs, whereas PD-1 binds programmed death ligand 1 (PD-L1) to prevent checkpoint activation and strengthen the cytotoxic T lymphocyte (CTL) response. The injection of humanized mice with DCs transduced with vector expressing CD40L and the HIV-1 SL9 epitope induced antigen-specific T cell proliferation and memory differentiation. Upon HIV-1 challenge of vaccinated mice, viral load was suppressed by 2 logs for 6 weeks. Introduction of the soluble PD-1 dimer into a vector that expressed full-length HIV-1 proteins accelerated the antiviral response. The results support development of this approach as a therapeutic vaccine that might allow HIV-1-infected individuals to control virus replication without antiretroviral therapy.
- Published
- 2019