Serum from convalescent Lassa fever patients was previously shown to be ineffective as a source of protective antibodies in some early studies. Subsequently, monoclonal antibodies (MAbs) to the Lassa virus (LASV) glycoprotein produced by memory B cells of West African patients who survived Lassa fever were identified. Development of MAbs as potential Lassa immunotherapeutics was facilitated by structural studies and mutational analyses that identified protective epitopes on the prefusion form of the LASV glycoprotein. Human mAbs were screened for reactivity to different neutralizing epitopes, potency, and broad reactivity against multiple lineages of LASV. MAbs were downselected in a guinea pig model of Lassa fever. A cocktail of three human MAbs designated Arevirumab-3 rescued 100% of Cynomolgus macaques at advanced stages of disease more than a week post-infection. Antibody therapeutics may be further developed in clinical trials in endemic areas potentially offering a key treatment option for Lassa fever.

恢复性拉沙热患者的血清以前在某些早期研究中显示不能作为保护性抗体的来源。随后，鉴定了由在拉萨热中幸存的西非患者的记忆B细胞产生的针对拉萨病毒（LASV）糖蛋白的单克隆抗体（MAb）。通过结构研究和突变分析促进了单克隆抗体作为潜在的Lassa免疫疗法的发展，这些研究确定了LASV糖蛋白预融合形式上的保护性抗原决定簇。筛选人单克隆抗体与不同中和表位的反应性，效力以及对多种LASV谱系的广泛反应性。在拉沙热的豚鼠模型中，单克隆抗体的选择不高。命名为Arevirumab-3的三种人类单克隆抗体的混合物拯救了100％食蟹猕猴在疾病晚期，感染后一周以上。在流行地区的临床试验中可能会进一步开发抗体疗法，这可能为拉沙热提供关键的治疗选择。