呼吸道合胞病毒(RSV)和流感是世界范围内严重呼吸道疾病的最重要原因之一。尽管有临床需要,几十年来,开发针对这些病毒的可靠有效疫苗的障碍一直存在。克服这些障碍需要更好地了解人类免疫力以及这些病原体逃避免疫力的策略。虽然表面上相似,对RSV和流感的病毒学和宿主反应明显不同.流感在自然感染后诱导强大的菌株特异性免疫,尽管目前疫苗的保护作用是短暂的。相比之下,即使病毒株特异性保护在RSV后也是不完全的,目前还没有许可的RSV疫苗.尽管动物模型对于开发对抗病毒免疫的基本理解至关重要,推断人类疾病一直是个问题。只有随着最近的翻译进展(例如受控的人类感染模型和高维技术),在人类环境中才开始阐明与流感相比对RSV的保护差异的机制。流感感染引起高亲和力IgA在呼吸道和病毒特异性IgG,这与保护有关。长寿的流感特异性T细胞也已被证明可以改善疾病。这种强大的免疫力促进了导致免疫逃逸的抗原变体的快速出现。RSV明显不同,尽管自然感染诱导高水平的针对保守抗原的抗体,但仍发生类似菌株的再感染。因此,RSV的免疫调节机制在抑制长期保护方面非常有效,随着I型干扰素信号的干扰,抗原呈递和趋化因子诱导的炎症可能都有作用。这些导致对适应性免疫的广泛影响,具有受损的B细胞记忆和减少的T细胞产生和功能。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,我们关注先天免疫识别的差异;每种病毒用于逃避这些早期免疫反应的策略;以及可能阻止长寿命记忆生成的先天-适应性界面的影响.因此,通过比较这些全球重要的病原体,我们重点介绍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.