4.7 Article

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

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COMMUNICATIONS BIOLOGY
卷 4, 期 1, 页码 -

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NATURE RESEARCH
DOI: 10.1038/s42003-021-02251-6

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  1. UtechS Photonic BioImaging (PBI) platform, a member of the France Life Imaging network [ANR-11-INBS-0006]
  2. Institut Carnot Pasteur Microbes Sante
  3. European Union [665807]
  4. Programs Transversaux de Recherche (PTR) from Institut Pasteur [52-17]

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Utilizing a lentiviral vector system with a human beta 2-microglobulin promoter, researchers found that the lentiviral-based vaccine outperformed the Ad5 'gold-standard' in mice and rats by inducing a polyfunctional and long-lived immune response.
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.

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