A lentiviral vector expressing a dendritic cell-targeting multimer induces mucosal anti-mycobacterial CD4+ T-cell immunity - Archive ouverte HAL Access content directly
Journal Articles Mucosal Immunology Year : 2022

A lentiviral vector expressing a dendritic cell-targeting multimer induces mucosal anti-mycobacterial CD4+ T-cell immunity

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François Anna

Abstract

Abstract Most viral vectors, including the potently immunogenic lentiviral vectors (LVs), only poorly direct antigens to the MHC-II endosomal pathway and elicit CD4 + T cells. We developed a new generation of LVs encoding antigen-bearing monomers of collectins substituted at their C-terminal domain with the CD40 ligand ectodomain to target and activate antigen-presenting cells. Host cells transduced with such optimized LVs secreted soluble collectin-antigen polymers with the potential to be endocytosed in vivo and reach the MHC-II pathway. In the murine tuberculosis model, such LVs induced efficient MHC-II antigenic presentation and triggered both CD8 + and CD4 + T cells at the systemic and mucosal levels. They also conferred a significant booster effect, consistent with the importance of CD4 + T cells for protection against Mycobacterium tuberculosis . Given the pivotal role of CD4 + T cells in orchestrating innate and adaptive immunity, this strategy could have a broad range of applications in the vaccinology field.
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Dates and versions

pasteur-03909615 , version 1 (21-12-2022)

Licence

Attribution - CC BY 4.0

Identifiers

Cite

François Anna, Jodie Lopez, Fanny Moncoq, Catherine Blanc, Pierre Authié, et al.. A lentiviral vector expressing a dendritic cell-targeting multimer induces mucosal anti-mycobacterial CD4+ T-cell immunity. Mucosal Immunology, 2022, 15 (6), pp.1389-1404. ⟨10.1038/s41385-022-00566-z⟩. ⟨pasteur-03909615⟩
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