Antibodies against viral pathogens represent promising therapeutic agents for the control of infection, and their antiviral efficacy has been shown to require the coordinated function of both the Fab and Fc domains 1 . The Fc domain engages a wide spectrum of receptors on discrete cells of the immune system to trigger the clearance of viruses and subsequent killing of infected cells 1 – 4 . Here we report that Fc engineering of anti-influenza IgG monoclonal antibodies for selective binding to the activating Fcγ receptor FcγRIIa results in enhanced ability to prevent or treat lethal viral respiratory infection in mice, with increased maturation of dendritic cells and the induction of protective CD8 + T cell responses. These findings highlight the capacity for IgG antibodies to induce protective adaptive immunity to viral infection when they selectively activate a dendritic cell and T cell pathway, with important implications for the development of therapeutic antibodies with improved antiviral efficacy against viral respiratory pathogens. An antibody Fc domain variant with enhanced binding to an activating Fc receptor on dendritic cells promotes the induction of a protective CD8 T cell response.

中文翻译：

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Fc 优化抗体引发对病毒性呼吸道感染的 CD8 免疫

针对病毒病原体的抗体代表了用于控制感染的有希望的治疗剂，并且它们的抗病毒功效已被证明需要 Fab 和 Fc 结构域 1 的协调功能。Fc 结构域与免疫系统离散细胞上的广泛受体结合，以触发病毒清除和随后杀死受感染细胞 1 – 4 。在这里，我们报告了用于选择性结合活化 Fcγ 受体 FcγRIIa 的抗流感 IgG 单克隆抗体的 Fc 工程导致预防或治疗小鼠致死性病毒性呼吸道感染的能力增强，树突状细胞的成熟增加和保护性 CD8 + 的诱导T细胞反应。这些发现强调了 IgG 抗体在选择性激活树突状细胞和 T 细胞途径时诱导对病毒感染的保护性适应性免疫的能力，这对于开发具有提高的抗病毒性呼吸道病原体的抗病毒功效的治疗性抗体具有重要意义。与树突状细胞上的活化 Fc 受体结合增强的抗体 Fc 结构域变体促进了保护性 CD8 T 细胞反应的诱导。