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一种表达树突状细胞靶向多聚体的慢病毒载体诱导黏膜抗分枝杆菌 CD4 T 细胞免疫。

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

机构信息

Pasteur-TheraVectys Joint Lab, Institut Pasteur, Université Paris Cité, 28 rue du Dr. Roux, F-75015, Paris, France.

Integrated Mycobacterial Pathogenomics Unit, CNRS UMR 3525, Institut Pasteur, Université Paris Cité, 25 rue du Dr. Roux, F-75015, Paris, France.

出版信息

Mucosal Immunol. 2022 Jun;15(6):1389-1404. doi: 10.1038/s41385-022-00566-z. Epub 2022 Sep 14.

DOI:10.1038/s41385-022-00566-z
PMID:36104497
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9473479/
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.

摘要

大多数病毒载体，包括具有强大免疫原性的慢病毒载体（LVs），只能将抗原低效地引导到 MHC-II 内体途径，并引发 CD4 T 细胞反应。我们开发了新一代的 LVs，其编码带有抗原的凝聚素单体，在 C 末端结构域用 CD40 配体的胞外结构域取代，以靶向和激活抗原呈递细胞。用这种优化的 LVs 转导的宿主细胞分泌可溶性凝聚素-抗原聚合物，具有体内被内吞和进入 MHC-II 途径的潜力。在小鼠结核病模型中，这种 LVs 诱导了有效的 MHC-II 抗原呈递，并在全身和黏膜水平触发了 CD8 和 CD4 T 细胞。它们还赋予了显著的增强效果，与 CD4 T 细胞在保护结核分枝杆菌方面的重要性一致。鉴于 CD4 T 细胞在协调先天和适应性免疫中的关键作用，这种策略在疫苗学领域可能具有广泛的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87fe/9705239/4aca87aba22c/41385_2022_566_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87fe/9705239/697e89b485ee/41385_2022_566_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87fe/9705239/4aca87aba22c/41385_2022_566_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87fe/9705239/c8d4c5466967/41385_2022_566_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87fe/9705239/8a74acad3546/41385_2022_566_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87fe/9705239/58b326609a27/41385_2022_566_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87fe/9705239/ce92eda1c81f/41385_2022_566_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87fe/9705239/0658949db2a6/41385_2022_566_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87fe/9705239/9ec2b1414915/41385_2022_566_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87fe/9705239/697e89b485ee/41385_2022_566_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87fe/9705239/4aca87aba22c/41385_2022_566_Fig8_HTML.jpg

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