期刊
MUCOSAL IMMUNOLOGY
卷 15, 期 6, 页码 1389-1404出版社
SPRINGERNATURE
DOI: 10.1038/s41385-022-00566-z
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资金
- Programmes Transversaux de Recherche (PTR) from Institut Pasteur [52-17]
- EU program TBVAC2020 [643381]
- CNRS, University of Toulouse, Agence Nationale de la Recherche/Program d'Investissements d'Avenir [ANR-11-EQUIPEX-0003]
- Fondation pour la Recherche Medicale [DEQ20160334902]
- Bettencourt Schueller Foundation
A new generation of lentiviral vectors has been developed to effectively activate antigen-presenting cells, inducing immune responses in both CD8(+) and CD4(+) T cells in a murine tuberculosis model, with a significant booster effect.
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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