Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA.
Cell Rep. 2021 May 4;35(5):109086. doi: 10.1016/j.celrep.2021.109086.
New World hantaviruses (NWHs) are endemic in North and South America and cause hantavirus cardiopulmonary syndrome (HCPS), with a case fatality rate of up to 40%. Knowledge of the natural humoral immune response to NWH infection is limited. Here, we describe human monoclonal antibodies (mAbs) isolated from individuals previously infected with Sin Nombre virus (SNV) or Andes virus (ANDV). Most SNV-reactive antibodies show broad recognition and cross-neutralization of both New and Old World hantaviruses, while many ANDV-reactive antibodies show activity for ANDV only. mAbs ANDV-44 and SNV-53 compete for binding to a distinct site on the ANDV surface glycoprotein and show potently neutralizing activity to New and Old World hantaviruses. Four mAbs show therapeutic efficacy at clinically relevant doses in hamsters. These studies reveal a convergent and potently neutralizing human antibody response to NWHs and suggest therapeutic potential for human mAbs against HCPS.
新型世界汉坦病毒（NWH）在北美洲和南美洲流行，引起汉坦病毒心肺综合征（HCPS），死亡率高达 40%。人们对 NWH 感染的自然体液免疫反应知之甚少。本研究描述了从先前感染过辛诺柏病毒（SNV）或安第斯病毒（ANDV）的个体中分离出的人源单克隆抗体（mAb）。大多数 SNV 反应性抗体显示出对新旧世界汉坦病毒的广泛识别和交叉中和作用，而许多 ANDV 反应性抗体仅对 ANDV 具有活性。mAb ANDV-44 和 SNV-53 竞争结合 ANDV 表面糖蛋白上的一个独特位点，并对新旧世界汉坦病毒表现出强大的中和活性。4 种 mAb 在临床相关剂量的仓鼠中显示出治疗效果。这些研究揭示了针对 NWH 的趋同且具有强大中和作用的人类抗体反应，并表明针对 HCPS 的人源 mAb 具有治疗潜力。
