CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, China.
Nat Microbiol. 2019 Jul;4(7):1231-1241. doi: 10.1038/s41564-019-0411-z. Epub 2019 Apr 1.
Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that causes substantial morbidity and mortality in livestock and humans. To date, there are no licensed human vaccines or therapeutics available. Here, we report the isolation of monoclonal antibodies from a convalescent patient, targeting the RVFV envelope proteins Gn and Gc. The Gn-specific monoclonal antibodies exhibited much higher neutralizing activities in vitro and protection efficacies in mice against RVFV infection, compared to the Gc-specific monoclonal antibodies. The Gn monoclonal antibodies were found to interfere with soluble Gn binding to cells and prevent infection by blocking the attachment of virions to host cells. Structural analysis of Gn complexed with four Gn-specific monoclonal antibodies resulted in the definition of three antigenic patches (A, B and C) on Gn domain I. Both patches A and B are major neutralizing epitopes. Our results highlight the potential of antibody-based therapeutics and provide a structure-based rationale for designing vaccines against RVFV.
裂谷热病毒（RVFV）是一种通过蚊子传播的病原体，可导致牲畜和人类出现大量发病率和死亡率。迄今为止，尚无获得许可的人类疫苗或疗法。在这里，我们报告了从恢复期患者中分离出针对 RVFV 包膜蛋白 Gn 和 Gc 的单克隆抗体。与 Gc 特异性单克隆抗体相比，Gn 特异性单克隆抗体在体外具有更高的中和活性和对 RVFV 感染的保护效力。发现 Gn 单克隆抗体可干扰可溶性 Gn 与细胞的结合，并通过阻止病毒粒子附着到宿主细胞来阻止感染。与四种 Gn 特异性单克隆抗体复合的 Gn 的结构分析导致在 Gn 结构域 I 上定义了三个抗原斑块（A、B 和 C）。斑块 A 和 B 都是主要的中和表位。我们的研究结果突出了基于抗体的治疗方法的潜力，并为设计针对 RVFV 的疫苗提供了基于结构的依据。
