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一种结核分枝杆菌特异性亚单位疫苗，与卡介苗联合使用可提供协同免疫。

A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin.

机构信息

Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.

Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.

出版信息

Nat Commun. 2021 Nov 18;12(1):6658. doi: 10.1038/s41467-021-26934-0.

DOI:10.1038/s41467-021-26934-0
PMID:34795205
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8602668/
Abstract

Given the encouraging clinical results of both candidate subunit vaccines and revaccination with Bacillus Calmette-Guérin (BCG) against tuberculosis (TB), there is support for combining BCG and subunit vaccination for increased efficacy. BCG and Mycobacterium tuberculosis (Mtb) share ~98% of their genome and current subunit vaccines are almost exclusively designed as BCG boosters. The goal of this study is to design a TB subunit vaccine composed of antigens not shared with BCG and explore the advantages of this design in a BCG + subunit co-administration vaccine strategy. Eight protective antigens are selected to create an Mtb-specific subunit vaccine, named H107. Whereas traditional vaccines containing BCG-shared antigens exhibit in vivo cross-reactivity to BCG, H107 shows no cross-reactivity and does not inhibit BCG colonization. Instead, co-administering H107 with BCG leads to increased adaptive responses against both H107 and BCG. Importantly, rather than expanding BCG-primed T cells, H107 broadens the overall vaccine repertoire with new T cell clones and introduces 'adjuvant-imprinted' qualities including Th17 responses and less-differentiated Th1 cells. Collectively, these features of H107 are associated with a substantial increase in long-term protection.

摘要

鉴于候选亚单位疫苗和卡介苗（BCG）复种在结核病（TB）方面的令人鼓舞的临床结果，支持联合使用 BCG 和亚单位疫苗以提高疗效。BCG 和结核分枝杆菌（Mtb）共享约 98%的基因组，目前的亚单位疫苗几乎完全是作为 BCG 增强剂设计的。本研究的目的是设计一种由与 BCG 不共享的抗原组成的 TB 亚单位疫苗，并探讨这种设计在 BCG+亚单位联合给药疫苗策略中的优势。选择了 8 种保护性抗原来创建一种名为 H107 的 Mtb 特异性亚单位疫苗。而含有 BCG 共享抗原的传统疫苗在体内对 BCG 表现出交叉反应性，H107 则没有交叉反应性，也不会抑制 BCG 定植。相反，与 BCG 联合使用 H107 会导致针对 H107 和 BCG 的适应性反应增加。重要的是，H107 没有扩大 BCG 启动的 T 细胞，而是通过新的 T 细胞克隆扩展了整体疫苗库，并引入了“佐剂印记”特性，包括 Th17 反应和分化程度较低的 Th1 细胞。总的来说，H107 的这些特征与长期保护的显著增加有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5424/8602668/8183e0c966dc/41467_2021_26934_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5424/8602668/2f61f89af2ff/41467_2021_26934_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5424/8602668/41f40d6a1fe0/41467_2021_26934_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5424/8602668/c8dd090f8ac9/41467_2021_26934_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5424/8602668/b69c6cec66b4/41467_2021_26934_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5424/8602668/ac88c7cafce7/41467_2021_26934_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5424/8602668/8183e0c966dc/41467_2021_26934_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5424/8602668/2f61f89af2ff/41467_2021_26934_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5424/8602668/41f40d6a1fe0/41467_2021_26934_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5424/8602668/c8dd090f8ac9/41467_2021_26934_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5424/8602668/b69c6cec66b4/41467_2021_26934_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5424/8602668/ac88c7cafce7/41467_2021_26934_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5424/8602668/8183e0c966dc/41467_2021_26934_Fig6_HTML.jpg

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