Mosquito inoculation of humans with arthritogenic alphaviruses results in a febrile syndrome characterized by debilitating musculoskeletal pain and arthritis. Despite an expanding global disease burden, no approved therapies or licensed vaccines exist. Here, we describe human monoclonal antibodies (mAbs) that bind to and neutralize multiple distantly related alphaviruses. These mAbs compete for an antigenic site and prevent attachment to the recently discovered Mxra8 alphavirus receptor. Three cryoelectron microscopy structures of Fab in complex with Ross River (RRV), Mayaro, or chikungunya viruses reveal a conserved footprint of the broadly neutralizing mAb RRV-12 in a region of the E2 glycoprotein B domain. This mAb neutralizes virus in vitro by preventing virus entry and spread and is protective in vivo in mouse models. Thus, the RRV-12 mAb and its defined epitope have potential as a therapeutic agent or target of vaccine design against multiple emerging arthritogenic alphavirus infections.

人类用致关节炎甲病毒接种蚊子会导致发热综合征，其特征是使人衰弱的肌肉骨骼疼痛和关节炎。尽管全球疾病负担不断扩大，但尚不存在获得批准的疗法或获得许可的疫苗。在这里，我们描述了结合并中和多种远缘甲病毒的人单克隆抗体 (mAb)。这些 mAb 竞争抗原位点并阻止附着于最近发现的 Mxra8 甲病毒受体。与罗斯河 (RRV)、Mayaro 或基孔肯雅病毒复合的 Fab 的三个冷冻电子显微镜结构揭示了广泛中和的 mAb RRV-12 在 E2 糖蛋白 B 结构域区域中的保守足迹。这种 mAb通过阻止病毒进入和传播来在体外中和病毒，并且具有保护作用体内小鼠模型。因此，RRV-12 mAb 及其确定的表位具有作为治疗剂或疫苗设计靶点的潜力，可针对多种新出现的致关节炎甲病毒感染。