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不同剂量 BCG 在 BALB/c 和 CB6F1 小鼠中对 H37Rv 或 Beijing HN878 攻击的效力和免疫原性。

Efficacy and immunogenicity of different BCG doses in BALB/c and CB6F1 mice when challenged with H37Rv or Beijing HN878.

机构信息

Bacteriology Division, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK.

Department of Bacteriology, Animal and Plant Health Agency, Addlestone, Surrey, KT15 3NB, UK.

出版信息

Sci Rep. 2021 Dec 2;11(1):23308. doi: 10.1038/s41598-021-02442-5.

DOI:10.1038/s41598-021-02442-5
PMID:34857776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8639814/
Abstract

Two strains of mice (BALB/c and CB6F1) were vaccinated with a range of Bacille Calmette-Guérin (BCG) Danish doses from 3 × 10 to 30 CFU/mouse, followed by aerosol infection with Mtb (H37Rv or West-Beijing HN878 strain). The results indicated that both strains of mice when infected with HN878 exhibited significant protection in their lungs with BCG doses at 3 × 10-3000 CFU (BALB/c) and 3 × 10-300 CFU (CB6F1). Whereas, a significant protection was seen in both strains of mice with BCG doses at 3 × 10-300 CFU when infected with H37Rv. A significant increase in the frequencies of BCG-specific IFNγ IL2 TNFα CD4 T cells in the BCG doses at 3 × 10-3000 CFU (BALB/c) and 3 × 10-300 CFU (CB6F1) was seen. The IFNγ IL2 TNFα CD4 T cells correlated with the Mtb burden in the lungs of HN878 infected mice (BALB/c and CB6F1) whereas, IFNγ TNFα CD4 T cells correlated with the BALB/c mice infected with H37Rv or HN878. The BCG dose at 3000 CFU (an equivalent single human dose in the mice by body weight) is protective in both strains of mice infected with H37Rv or HN878 and may serve an interesting dose to test new TB vaccine in a preclinical animal model.

摘要

两种品系的小鼠(BALB/c 和 CB6F1)用一系列卡介苗(BCG)丹麦剂量(3×10 至 3000 CFU/只)进行了疫苗接种,然后用结核分枝杆菌(H37Rv 或西方-北京 HN878 株)气溶胶感染。结果表明,当用 HN878 感染时,两种小鼠品系在肺部均显示出对 3×10-3000 CFU(BALB/c)和 3×10-300 CFU(CB6F1)剂量的 BCG 的显著保护作用。而当用 H37Rv 感染时,两种小鼠品系均显示出对 3×10-300 CFU 剂量的 BCG 的显著保护作用。在 3×10-3000 CFU(BALB/c)和 3×10-300 CFU(CB6F1)剂量的 BCG 中,BCG 特异性 IFNγ、IL2、TNFα CD4 T 细胞的频率显著增加。IFNγ、IL2、TNFα CD4 T 细胞与 HN878 感染小鼠肺部的 Mtb 负担相关(BALB/c 和 CB6F1),而 IFNγ TNFα CD4 T 细胞与 H37Rv 或 HN878 感染的 BALB/c 小鼠相关。3000 CFU(按体重计算,相当于小鼠体内的单个人剂量)的 BCG 剂量对感染 H37Rv 或 HN878 的两种小鼠品系均具有保护作用,并且可能是一种有趣的剂量,可以在临床前动物模型中测试新的结核病疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8372/8639814/91597ab6dfd0/41598_2021_2442_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8372/8639814/75f17cc15f26/41598_2021_2442_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8372/8639814/d48ee16e5502/41598_2021_2442_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8372/8639814/605f65906404/41598_2021_2442_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8372/8639814/91597ab6dfd0/41598_2021_2442_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8372/8639814/75f17cc15f26/41598_2021_2442_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8372/8639814/d48ee16e5502/41598_2021_2442_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8372/8639814/605f65906404/41598_2021_2442_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8372/8639814/91597ab6dfd0/41598_2021_2442_Fig4_HTML.jpg

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Animal Models of Mycobacteria Infection.分枝杆菌感染的动物模型
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Adaption of the ex vivo mycobacterial growth inhibition assay for use with murine lung cells.用于鼠肺细胞的体外分枝杆菌生长抑制试验的适应。
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卡介苗接种后进行BAFF和APRIL免疫疗法可增强小鼠对肺结核的抵抗力。
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Interrupted BCG vaccination is a major threat to global child health.卡介苗接种中断对全球儿童健康构成重大威胁。
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