A lentiviral vector expressing a dendritic cell-targeting multimer induces mucosal anti-mycobacterial CD4 + T-cell immunity.
François AnnaJodie LopezFanny MoncoqCatherine BlancPierre AuthiéAmandine NoiratIngrid FertPhilippe SouqueFabien NevoAlexandre PawlikDavid HardySophie GoyardDenis HudrisierRoland BroschFrançoise GuinetOlivier NeyrollesPierre CharneauLaleh MajlessiPublished in: Mucosal immunology (2022)
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.
Keyphrases
- mycobacterium tuberculosis
- induced apoptosis
- dendritic cells
- cell cycle arrest
- immune response
- sars cov
- endoplasmic reticulum stress
- pulmonary tuberculosis
- emergency department
- case report
- high glucose
- signaling pathway
- regulatory t cells
- cancer therapy
- drug delivery
- endothelial cells
- nk cells
- cell proliferation
- hiv aids
- adverse drug
- electronic health record
- molecular dynamics simulations