Lentiviral vector induces high-quality memory T cells via dendritic cells transduction

We report a lentiviral vector harboring the human beta 2-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 beta 2-microglobulin promoter represents a promising approach to produce long-lasting, high-quality cellular immunity for vaccinal purposes. Ku et al. report a lentiviral (LV) vector system in which expression of vaccine antigens is driven by beta 2-microglobulin (beta 2m) promoter. Conducting comparative studies in mice and rats, they find that LV-based vaccine outperforms the 'gold-standard' Ad5 by inducing a polyfunctional and long-lived immune response.