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Exploiting Pre-Existing CD4+ T Cell Help from Bacille Calmette–Guérin Vaccination to Improve Antiviral Antibody Responses
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-06-08 , DOI: 10.4049/jimmunol.2000191
Tony W Ng 1 , Ariel S Wirchnianski 1 , Anna Z Wec 1, 2 , J Maximilian Fels 1 , Christopher T Johndrow 1 , Kevin O Saunders 3 , Hua-Xin Liao 3 , John Chan 1, 4 , William R Jacobs 1 , Kartik Chandran 1 , Steven A Porcelli 4, 5
Affiliation  

Key Points BCG vaccination induced a broad range of Th subtypes, including Th1 and Tfh. Vaccine design with BCG epitopes used BCG Th cells to drive Ab responses. Prior BCG exposure can be exploited in a general approach to improve vaccine design. Visual Abstract The continuing emergence of viral pathogens and their rapid spread into heavily populated areas around the world underscore the urgency for development of highly effective vaccines to generate protective antiviral Ab responses. Many established and newly emerging viral pathogens, including HIV and Ebola viruses, are most prevalent in regions of the world in which Mycobacterium tuberculosis infection remains endemic and vaccination at birth with M. bovis bacille Calmette–Guérin (BCG) is widely used. We have investigated the potential for using CD4+ T cells arising in response to BCG as a source of help for driving Ab responses against viral vaccines. To test this approach, we designed vaccines comprised of protein immunogens fused to an immunodominant CD4+ T cell epitope of the secreted Ag 85B protein of BCG. Proof-of-concept experiments showed that the presence of BCG-specific Th cells in previously BCG-vaccinated mice had a dose-sparing effect for subsequent vaccination with fusion proteins containing the Ag 85B epitope and consistently induced isotype switching to the IgG2c subclass. Studies using an Ebola virus glycoprotein fused to the Ag 85B epitope showed that prior BCG vaccination promoted high-affinity IgG1 responses that neutralized viral infection. The design of fusion protein vaccines with the ability to recruit BCG-specific CD4+ Th cells may be a useful and broadly applicable approach to generating improved vaccines against a range of established and newly emergent viral pathogens.

中文翻译:

利用卡介苗-Guérin 疫苗接种中预先存在的 CD4+ T 细胞帮助来改善抗病毒抗体反应

要点 BCG 疫苗接种诱导了广泛的 Th 亚型,包括 Th1 和 Tfh。具有 BCG 表位的疫苗设计使用 BCG Th 细胞来驱动 Ab 反应。可以在一般方法中利用先前的 BCG 暴露来改进疫苗设计。视觉摘要 病毒病原体的不断出现及其在世界各地人口稠密地区的迅速传播凸显了开发高效疫苗以产生保护性抗病毒抗体反应的紧迫性。许多已建立和新出现的病毒病原体,包括 HIV 和埃博拉病毒,在世界上最流行的地区,结核分枝杆菌感染仍然流行,出生时接种牛分枝杆菌卡介苗 (BCG) 疫苗被广泛使用。我们已经研究了使用响应 BCG 产生的 CD4+ T 细胞作为驱动针对病毒疫苗的抗体反应的帮助来源的潜力。为了测试这种方法,我们设计了由蛋白质免疫原组成的疫苗,这些蛋白质免疫原与 BCG 分泌的 Ag 85B 蛋白的免疫显性 CD4+ T 细胞表位融合。概念验证实验表明,在先前接种 BCG 的小鼠中,BCG 特异性 Th 细胞的存在对随后接种含有 Ag 85B 表位的融合蛋白具有剂量节约效应,并始终诱导同种型转换为 IgG2c 亚类。使用与 Ag 85B 表位融合的埃博拉病毒糖蛋白的研究表明,先前的 BCG 疫苗接种促进了中和病毒感染的高亲和力 IgG1 反应。
更新日期:2020-06-08
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