OBJECTIVES Influenza causes a spectrum of disease from asymptomatic infection to fatal outcome, and pre-existing immunity can alter susceptibility and disease severity. In a household transmission study, we recruited outpatients with confirmed influenza virus infection and prospectively identified secondary infections in their household contacts, therefore identifying infection cases with baseline samples for determining immune-mediated protection from influenza infection. METHODS We examined baseline broadly reactive immune correlates of relevance to universal vaccine development, specifically antibody-dependent cytotoxic (ADCC) antibodies and T-cell responses in functional assays. Antibodies were assessed in a cell-based NK cell degranulation assay by flow cytometry, and T-cell responses were assessed by IFN-γ intracellular cytokine staining flow cytometry assay. RESULTS The magnitude of antibody responses and ADCC function for multiple influenza-specific proteins was lower in participants who became infected, consolidating the role of pre-existing antibodies in protection from seasonal influenza virus infection. Among H1N1-infected contacts, we found that higher levels of pre-existing H1-haemagglutinin ADCC responses correlated with reduced symptom severity. Recent infection boosted the titre and magnitude of haemagglutinin-, neuraminidase- and nucleoprotein-specific ADCC antibodies. Limited T-cell samples precluded conclusions on the role of pre-existing T-cell responses. CONCLUSIONS Overall, ADCC responses are a protective correlate against influenza virus infection that should be considered in future vaccine development and evaluation.Influenza-specific ADCC responses are elevated in uninfected subjects, associated with reduced symptoms and boosted by recent infection, whilst HA stem and NA IgG are also elevated in uninfected participants irrespective of ADCC function.

中文翻译：

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在一项关于流感传播的家庭研究中，最近感染增加了交叉反应性抗体依赖性细胞毒性抗体。

目标 流感会导致一系列疾病，从无症状感染到致命结果，预先存在的免疫力可以改变易感性和疾病严重程度。在一项家庭传播研究中，我们招募了确诊流感病毒感染的门诊患者，并前瞻性地确定了其家庭接触者中的继发感染，因此确定了具有基线样本的感染病例，以确定免疫介导的流感感染保护。方法 我们检查了与通用疫苗开发相关的基线广泛反应性免疫相关性，特别是功能测定中的抗体依赖性细胞毒性 (ADCC) 抗体和 T 细胞反应。通过流式细胞术在基于细胞的 NK 细胞脱粒试验中评估抗体，通过 IFN-γ 细胞内细胞因子染色流式细胞术测定评估 T 细胞反应。结果 在被感染的参与者中，多种流感特异性蛋白的抗体反应幅度和 ADCC 功能较低，巩固了先前存在的抗体在保护免受季节性流感病毒感染方面的作用。在 H1N1 感染的接触者中，我们发现较高水平的预先存在的 H1-血凝素 ADCC 反应与症状严重程度降低相关。最近的感染提高了血凝素、神经氨酸酶和核蛋白特异性 ADCC 抗体的滴度和强度。有限的 T 细胞样本排除了关于预先存在的 T 细胞反应的作用的结论。结论 总体而言，