Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA; Galveston National Laboratory, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Curr Opin Virol. 2019 Aug;37:97-104. doi: 10.1016/j.coviro.2019.07.003. Epub 2019 Aug 8.
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.
先前的一些早期研究表明，恢复期拉沙热患者的血清作为保护性抗体的来源是无效的。随后，从幸存拉沙热的西非患者的记忆 B 细胞中产生的抗拉沙病毒 (LASV) 糖蛋白的单克隆抗体 (MAb) 被鉴定出来。通过结构研究和突变分析，确定了 LASV 糖蛋白预融合形式上的保护性表位，这有助于 MAbs 作为潜在的拉沙免疫疗法的发展。筛选了人类 mAb 对不同中和表位的反应性、效力和对多种 LASV 谱系的广泛反应性。MAb 在拉沙热豚鼠模型中进行了选择。三种指定为 Arevirumab-3 的人源 mAb 鸡尾酒在感染后一周以上的疾病晚期挽救了 100%的食蟹猴。抗体疗法可能会在流行地区的临床试验中进一步开发，为拉沙热提供一种潜在的关键治疗选择。
