小鼠接种腺病毒血清 26 型载体疫苗引起的免疫反应的早期时空演变。

IF 4 2区 医学 Q2 VIROLOGY
Eryn Blass, Alessandro Colarusso, Malika Aid, Rafael A Larocca, R Keith Reeves, Dan H Barouch
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引用次数: 0

摘要

作为免疫挑战的第一反应者,先天免疫系统形成并调节随后的适应性免疫反应。许多评估先天免疫在启动疫苗引发的适应性免疫反应中的作用的临床研究很大程度上局限于血液,因为获取组织样本本身就很困难。然而,缺乏疫苗部位和引流淋巴结信息限制了对疫苗接种引起的早期事件的理解,这些事件可能会影响疫苗引起的免疫。因此,我们利用小鼠模型来研究肌肉注射血清型26腺病毒(Ad26)载体接种组织后24小时内免疫反应的时空演变。通过检测细胞因子、趋化因子、细胞反应和转录组学途径,我们发现Ad26疫苗引发的先天免疫反应在1小时内开始,并在前24小时内在组织和血液中迅速发展。此外,疫苗接种后6小时血清IL-6、MIG、MIP-1α、MIP-1β和TNF-α水平与疫苗接种后60天血液和组织中疫苗引发的记忆性CD8+ T细胞应答频率相关。综上所述,我们的数据表明,对Ad26载体疫苗接种的免疫反应在组织中1小时内迅速开始,早在疫苗接种后6小时发生的事件可以在较晚的记忆时间点形成疫苗引发的CD8+ T细胞反应。先前的研究主要集中在接种疫苗后外周血中的先天免疫激活。在这项研究中,我们报告了Ad26疫苗接种后小鼠组织中详细的空间和时间先天免疫激活。我们观察到快速先天激活不仅在外周血,而且在引流淋巴结和接种部位。我们的研究结果提供了宿主对疫苗接种反应比以前报道的更详细的图片。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Early spatiotemporal evolution of the immune response elicited by adenovirus serotype 26 vector vaccination in mice.

As the first responder to immunological challenges, the innate immune system shapes and regulates the ensuing adaptive immune response. Many clinical studies evaluating the role of innate immunity in initiating vaccine-elicited adaptive immune responses have largely been confined to blood due to the inherent difficulty in acquiring tissue samples. However, the absence of vaccine-site and draining lymph node information limits the understanding of early events induced by vaccination that could potentially shape vaccine-elicited immunity. We, therefore, utilized a mouse model to investigate the spatiotemporal evolution of the immune response within the first 24 hours following intramuscular adenovirus serotype 26 (Ad26) vector vaccination in tissues. We show that the Ad26 vaccine-elicited innate immune response commences by 1 hour and rapidly evolves in tissues and blood within the first 24 hours, as reflected by the detection of cytokines, chemokines, cellular responses, and transcriptomic pathways. Furthermore, serum levels of IL-6, MIG, MIP-1α, MIP-1β, and TNF-α at 6 hours post-vaccination correlated with the frequency of vaccine-elicited memory CD8+ T cell responses evaluated at 60 days post-vaccination in blood and tissues. Taken together, our data suggest that the immune response to Ad26 vector vaccination commences quickly in tissues by 1 hour and that events by as early as 6 hours post-vaccination can shape vaccine-elicited CD8+ T cell responses at later memory time points.IMPORTANCEPrior studies have largely concentrated on innate immune activation in peripheral blood following vaccination. In this study, we report the detailed spatial and temporal innate immune activation in tissues following Ad26 vaccination in mice. We observed rapid innate activation not only in peripheral blood but also in draining lymph nodes and at the site of inoculation. Our findings provide a more detailed picture of the host response to vaccination than previously reported.

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来源期刊
Journal of Virology
Journal of Virology 医学-病毒学
CiteScore
10.10
自引率
7.40%
发文量
906
审稿时长
1 months
期刊介绍: Journal of Virology (JVI) explores the nature of the viruses of animals, archaea, bacteria, fungi, plants, and protozoa. We welcome papers on virion structure and assembly, viral genome replication and regulation of gene expression, genetic diversity and evolution, virus-cell interactions, cellular responses to infection, transformation and oncogenesis, gene delivery, viral pathogenesis and immunity, and vaccines and antiviral agents.
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