Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus.
Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus.
复制标题
DOI：
10.3389/fimmu.2018.00323
复制
发表时间：
2018
影响因子：
7.3
通讯作者：
Chiu C
中科院分区：
文献类型：
--
作者：
Ascough S;Paterson S;Chiu C
呼吸道合胞病毒（RSV）和流感是全球严重呼吸道疾病的最重要原因之一。尽管有临床需求，但数十年来，开发针对这些病毒的可靠有效疫苗的障碍仍然存在。克服这些障碍需要更好地了解人类免疫力和这些病原体逃避它的策略。尽管表面上相似，但病毒学和宿主对RSV和流感的反应截然不同。尽管当前疫苗的保护作用是短暂的，但流感在自然感染后会诱导强大的毒株特异性免疫。相比之下，在RSV之后，甚至毒株特异性保护也是不完整的，并且目前没有许可的RSV疫苗。虽然动物模型对于发展抗病毒免疫的基本理解至关重要，但推断人类疾病一直存在问题。只有随着最近的转化进展（如受控的人类感染模型和高维技术），才开始在人类背景下阐明与流感相比对RSV的保护差异的机制。流感感染在呼吸道中产生高亲和力伊加和病毒特异性IgG，这与保护有关。长寿命的流感特异性T细胞也被证明可以改善疾病。这种强大的免疫力促进抗原变体的快速出现，导致免疫逃逸。RSV明显不同，因为尽管自然感染诱导针对保守抗原的高水平抗体，但仍发生类似毒株的再感染。因此，RSV的免疫调节机制在抑制长期保护方面非常有效，I型干扰素信号传导、抗原呈递和趋化因子诱导的炎症的干扰可能都起作用。这些导致对适应性免疫的广泛影响，B细胞记忆受损，T细胞生成和功能降低。在这里，我们讨论了流感和RSV后临床结果和免疫反应的差异。具体来说，我们专注于它们被先天免疫识别的差异;每种病毒逃避这些早期免疫反应的策略;以及可能阻止长寿记忆产生的先天适应性界面的影响。因此，通过比较这些全球重要的病原体，我们强调了可以更好地诱导最佳抗病毒免疫的机制，并讨论了这些见解为新型疫苗提供信息的潜力。
Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV and there are currently no licensed RSV vaccines. Although animal models have been critical for developing a fundamental understanding of antiviral immunity, extrapolating to human disease has been problematic. It is only with recent translational advances (such as controlled human infection models and high-dimensional technologies) that the mechanisms responsible for differences in protection against RSV compared to influenza have begun to be elucidated in the human context. Influenza infection elicits high-affinity IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long-lived influenza-specific T cells have also been shown to ameliorate disease. This robust immunity promotes rapid emergence of antigenic variants leading to immune escape. RSV differs markedly, as reinfection with similar strains occurs despite natural infection inducing high levels of antibody against conserved antigens. The immunomodulatory mechanisms of RSV are thus highly effective in inhibiting long-term protection, with disturbance of type I interferon signaling, antigen presentation and chemokine-induced inflammation possibly all contributing. These lead to widespread effects on adaptive immunity with impaired B cell memory and reduced T cell generation and functionality. Here, we discuss the differences in clinical outcome and immune response following influenza and RSV. Specifically, we focus on differences in their recognition by innate immunity; the strategies used by each virus to evade these early immune responses; and effects across the innate-adaptive interface that may prevent long-lived memory generation. Thus, by comparing these globally important pathogens, we highlight mechanisms by which optimal antiviral immunity may be better induced and discuss the potential for these insights to inform novel vaccines.
影响因子：
11.8
作者：
Sridhar S;Begom S;Bermingham A;Hoschler K;Adamson W;Carman W;Van Kerkhove MD;Lalvani A
通讯作者：
Lalvani A