Respiratory syncytial virus (RSV) is increasingly recognized for causing severe morbidity and mortality in older adults, but there are few studies on the RSV-induced immune response in this population. Information on the immunological processes at play during RSV infection in specific risk groups is essential for the rational and targeted design of novel vaccines and therapeutics. Here, we assessed the antibody and local cytokine response to RSV infection in community-dwelling older adults (≥60 years of age). During three winters, serum and nasopharyngeal swab samples were collected from study participants during acute respiratory infection and recovery. RSV IgG enzyme-linked immunosorbent assays (ELISA) and virus neutralization assays were performed on serum samples from RSV-infected individuals (n = 41) and controls (n = 563 and n = 197, respectively). Nasal RSV IgA and cytokine concentrations were determined using multiplex immunoassays in a subset of participants. An in vitro model of differentiated primary bronchial epithelial cells was used to assess RSV-induced cytokine responses over time. A statistically significant increase in serum neutralization titers and IgG concentrations was observed in RSV-infected participants compared to controls. During acute RSV infection, a statistically significant local upregulation of beta interferon (IFN-β), IFN-λ1, IFN-γ, interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α), IL-6, IL-10, CXCL8, and CXCL10 was found. IFN-β, IFN-λ1, CXCL8, and CXCL10 were also upregulated in the epithelial model upon RSV infection. In conclusion, this study provides novel insights into the basic immune response to RSV infection in an important and understudied risk population, providing leads for future studies that are essential for the prevention and treatment of severe RSV disease in older adults.

中文翻译：

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社区老年人对呼吸道合胞病毒感染的抗体和局部细胞因子反应。

呼吸道合胞病毒 (RSV) 越来越多地被认为会导致老年人严重的发病率和死亡率，但很少有关于该人群中 RSV 诱导的免疫反应的研究。在特定风险群体中 RSV 感染期间发挥作用的免疫过程的信息对于合理和有针对性地设计新型疫苗和治疗方法至关重要。在这里，我们评估了社区老年人（≥60 岁）对 RSV 感染的抗体和局部细胞因子反应。在三个冬天，研究参与者在急性呼吸道感染和康复期间收集了血清和鼻咽拭子样本。对 RSV 感染个体的血清样本进行 RSV IgG 酶联免疫吸附测定 (ELISA) 和病毒中和测定 ( n= 41）和对照（分别为n = 563 和n = 197）。在一部分参与者中使用多重免疫测定法测定鼻 RSV IgA 和细胞因子浓度。一种在体外分化的原代支气管上皮细胞模型用于评估随时间推移的 RSV 诱导的细胞因子反应。与对照组相比，在 RSV 感染的参与者中观察到血清中和滴度和 IgG 浓度的统计学显着增加。在急性 RSV 感染期间，β 干扰素 (IFN-β)、IFN-λ1、IFN-γ、白细胞介素 1β (IL-1β)、肿瘤坏死因子 α (TNF-α)、IL-6、IL 的局部上调有统计学意义-10、CXCL8 和 CXCL10 被发现。IFN-β、IFN-λ1、CXCL8 和 CXCL10 在 RSV 感染后的上皮模型中也上调。总之，这项研究为重要但研究不足的风险人群对 RSV 感染的基本免疫反应提供了新的见解，