Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, Missouri, United States of America.
PLoS Pathog. 2019 Nov 7;15(11):e1008061. doi: 10.1371/journal.ppat.1008061. eCollection 2019 Nov.
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes persistent arthritis in a subset of human patients. We report the isolation and functional characterization of monoclonal antibodies (mAbs) from two patients infected with CHIKV in the Dominican Republic. Single B cell sorting yielded a panel of 46 human mAbs of diverse germline lineages that targeted epitopes within the E1 or E2 glycoproteins. MAbs that recognized either E1 or E2 proteins exhibited neutralizing activity. Viral escape mutations localized the binding epitopes for two E1 mAbs to sites within domain I or the linker between domains I and III; and for two E2 mAbs between the β-connector region and the B-domain. Two of the E2-specific mAbs conferred protection in vivo in a stringent lethal challenge mouse model of CHIKV infection, whereas the E1 mAbs did not. These results provide insight into human antibody response to CHIKV and identify candidate mAbs for therapeutic intervention.
基孔肯雅病毒（CHIKV）是一种经蚊子传播的甲病毒，可导致人类患者中的一部分人群出现持续性关节炎。我们报告了来自于两名在多米尼加共和国感染 CHIKV 的患者的单克隆抗体（mAb）的分离和功能特征。通过单细胞分选获得了一个由 46 种不同种系的人类 mAb 组成的面板，这些 mAb 针对 E1 或 E2 糖蛋白内的表位。既识别 E1 又识别 E2 蛋白的 mAb 具有中和活性。病毒逃逸突变将两个 E1 mAb 的结合表位定位在 I 结构域内或 I 结构域和 III 结构域之间的连接区；而两个 E2 mAb 的结合表位在β连接区和 B 结构域之间。两种 E2 特异性 mAb 在严格致死性挑战的 CHIKV 感染小鼠模型中具有体内保护作用，而 E1 mAb 则没有。这些结果提供了对人类针对 CHIKV 的抗体反应的深入了解，并确定了用于治疗干预的候选 mAb。
