Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Ragon Institute of MGH, MIT, and Harvard University, Cambridge, MA 02139, USA.
Sci Immunol. 2019 Feb 22;4(32). doi: 10.1126/sciimmunol.aav5062.
Chikungunya virus (CHIKV) is an emerging mosquito-borne virus that has caused explosive outbreaks worldwide. Although neutralizing monoclonal antibodies (mAbs) against CHIKV inhibit infection in animals, the contribution of Fc effector functions to protection remains unknown. Here, we evaluated the activity of therapeutic mAbs that had or lacked the ability to engage complement and Fcγ receptors (FcγR). When administered as post-exposure therapy in mice, the Fc effector functions of mAbs promoted virus clearance from infected cells and reduced joint swelling-results that were corroborated in antibody-treated transgenic animals lacking activating FcγR. The control of CHIKV infection by antibody-FcγR engagement was associated with an accelerated influx of monocytes. A series of immune cell depletions revealed that therapeutic mAbs required monocytes for efficient clearance of CHIKV infection. Overall, our study suggests that in mice, FcγR expression on monocytes is required for optimal therapeutic activity of antibodies against CHIKV and likely other related viruses.
基孔肯雅病毒（CHIKV）是一种新兴的蚊媒病毒，已在全球范围内引发了爆炸性的疫情。尽管针对 CHIKV 的中和单克隆抗体（mAbs）能抑制动物感染，但 Fc 效应功能对保护的贡献尚不清楚。在这里，我们评估了具有或缺乏结合补体和 Fcγ 受体（FcγR）能力的治疗性 mAbs 的活性。当作为暴露后治疗在小鼠中给药时，mAbs 的 Fc 效应功能促进了感染细胞中病毒的清除，并减少了关节肿胀——这些结果在缺乏激活型 FcγR 的抗体治疗转基因动物中得到了证实。抗体-FcγR 结合对 CHIKV 感染的控制与单核细胞的快速涌入有关。一系列免疫细胞耗竭显示，治疗性 mAbs 需要单核细胞才能有效清除 CHIKV 感染。总的来说，我们的研究表明，在小鼠中，FcγR 在单核细胞上的表达对于针对 CHIKV 及可能其他相关病毒的抗体的最佳治疗活性是必需的。
