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Abstract
We report a lentiviral vector harboring the human β2-microglobulin promoter, with predominant expression in immune cells and minimal proximal enhancers to improve vector safety. This lentiviral vector efficiently transduces major dendritic cell subsets in vivo. With a mycobacterial immunogen, we observed distinct functional signatures and memory phenotype in lentiviral vector- or Adenovirus type 5 (Ad5)-immunized mice, despite comparable antigen-specific CD8+ T cell magnitudes. Compared to Ad5, lentiviral vector immunization resulted in higher multifunctional and IL-2-producing CD8+ T cells. Furthermore, lentiviral vector immunization primed CD8+ T cells towards central memory phenotype, while Ad5 immunization favored effector memory phenotype. Studies using HIV antigens in outbred rats demonstrated additional clear-cut evidence for an immunogenic advantage of lentiviral vector over Ad5. Additionally, lentiviral vector provided enhance therapeutic anti-tumor protection than Ad5. In conclusion, coupling lentiviral vector with β2-microglobulin promoter represents a promising approach to produce long-lasting, high-quality cellular immunity for vaccinal purposes.
Highlights
We report a lentiviral vector harboring the human β2-microglobulin promoter, with predominant expression in immune cells and minimal proximal enhancers to improve vector safety
Towards better safety and immune response efficiency of lentiviral vector, we investigated the human β2m promoter, which comprises minimal proximal antigenpresenting cells (APCs)-specific enhancer elements and is widely active in immune cells, notably dendritic cells
To assess the efficacy of β2m promoter in dendritic cells, we transduced murine Bone marrow-derived dendritic cells with an integrative lentiviral vector coding for the reporter green fluorescent protein (GFP) at a multiplicity of infection (MOI) of 10, under the regulation of CMV (LV-CMV-GFP) or β2m (LV-β2m-GFP) promoter
Summary
We report a lentiviral vector harboring the human β2-microglobulin promoter, with predominant expression in immune cells and minimal proximal enhancers to improve vector safety. This lentiviral vector efficiently transduces major dendritic cell subsets in vivo. Immunization with viral vectors remains the most efficient strategy to induce CD8+ T-cell responses, having the edge over other molecular (e.g., DNA, RNA, and peptide) or cellular (e.g., dendritic cell-based, attenuated microorganism) vaccines[6]. Compared to other vaccine strategies, viral vectors efficiently deliver the transgene intracellularly, resulting in a sustained antigen expression. This favors the effective presentation through the major histocompatibility complex-I presentation machinery, initiating CD8+ T-cell responses. Lentiviral vectors are majorly pseudo-typed with heterologous vesicular stomatitis virus envelop glycoprotein (VSV-G), to which human populations have negligible exposure
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