Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell Rep. 2021 Apr 6;35(1):108962. doi: 10.1016/j.celrep.2021.108962.
Although neutralizing monoclonal antibodies (mAbs) against epitopes within the alphavirus E2 protein can protect against infection, the functional significance of non-neutralizing mAbs is poorly understood. Here, we evaluate the activity of 13 non-neutralizing mAbs against Mayaro virus (MAYV), an emerging arthritogenic alphavirus. These mAbs bind to the MAYV virion and surface of infected cells but fail to neutralize infection in cell culture. Mapping studies identify six mAb binding groups that localize to discrete epitopes within or adjacent to the A domain of the E2 glycoprotein. Remarkably, passive transfer of non-neutralizing mAbs protects against MAYV infection and disease in mice, and their efficacy requires Fc effector functions. Monocytes mediate the protection of non-neutralizing mAbs in vivo, as Fcγ-receptor-expressing myeloid cells facilitate the binding, uptake, and clearance of MAYV without antibody-dependent enhancement of infection. Humoral protection against alphaviruses likely reflects contributions from non-neutralizing antibodies through Fc-dependent mechanisms that accelerate viral clearance.
虽然针对黄病毒 E2 蛋白表位的中和单克隆抗体 (mAb) 可预防感染，但非中和 mAb 的功能意义仍知之甚少。在这里，我们评估了 13 种针对 Mayaro 病毒 (MAYV) 的非中和 mAb 的活性，MAYV 是一种新兴的致关节炎黄病毒。这些 mAb 结合到 MAYV 病毒粒子和感染细胞的表面，但不能在细胞培养中中和感染。作图研究确定了 6 个 mAb 结合组，它们定位于 E2 糖蛋白 A 结构域内或附近的离散表位上。值得注意的是，非中和 mAb 的被动转移可预防 MAYV 在小鼠中的感染和疾病，并且其功效需要 Fc 效应功能。单核细胞在体内介导非中和 mAb 的保护作用，因为 Fcγ 受体表达的髓样细胞促进 MAYV 的结合、摄取和清除，而不会增强抗体依赖性感染。针对黄病毒的体液保护可能反映了非中和抗体通过 Fc 依赖性机制的贡献，这些机制可加速病毒清除。
