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

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...

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Detalles Bibliográficos
Autores principales: Anna, François, Lopez, Jodie, Moncoq, Fanny, Blanc, Catherine, Authié, Pierre, Noirat, Amandine, Fert, Ingrid, Souque, Philippe, Nevo, Fabien, Pawlik, Alexandre, Hardy, David, Goyard, Sophie, Hudrisier, Denis, Brosch, Roland, Guinet, Françoise, Neyrolles, Olivier, Charneau, Pierre, Majlessi, Laleh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9473479/
https://www.ncbi.nlm.nih.gov/pubmed/36104497
http://dx.doi.org/10.1038/s41385-022-00566-z
Descripción
Sumario: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.