小柯机器人

美国爱因斯坦医学院Kartik Chandran等研究人员合作鉴定出克里米亚-刚果出血热的保护性中和抗体。相关论文于2021年6月1日在线发表于国际学术期刊《细胞》。

研究人员表征了人类对自然克里米亚-刚果出血热病毒（CCHFV）感染的免疫反应，并用于鉴定针对病毒糖蛋白的有效中和单克隆抗体（nAb）。竞争实验表明，这些nAb结合Gc亚基中的六个不同的抗原位点。这些位点通过诱变进一步描绘并映射到Gc的预融合模型上。筛选确定了提供协同中和作用的非竞争性nAb组合。

通过双特异性抗体（bsAb）工程，中和广度和效力得以进一步增强。尽管在暴露前或暴露后的预防环境中，多种nAb保护小鼠免受致命的CCHFV攻击，但只有一种bsAb（DVD-121-801）提供了治疗性保护。DVD-121-801是一种有前途的候选药物，可作为CCHFV治疗剂进行临床开发。

据了解，CCHFV是世界卫生组织的重点病原体。CCHFV感染引起高度致命的出血热，目前急需针对该病的特定治疗和疫苗。 

附：英文原文

Title: Protective neutralizing antibodies from human survivors of Crimean-Congo hemorrhagic fever

Author: J. Maximilian Fels, Daniel P. Maurer, Andrew S. Herbert, Ariel S. Wirchnianski, Olivia Vergnolle, Robert W. Cross, Dafna M. Abelson, Crystal L. Moyer, Akaash K. Mishra, Jennifer T. Aguilan, Ana I. Kuehne, Noel T. Pauli, Russell R. Bakken, Elisabeth K. Nyakatura, Jan Hellert, Gregory Quevedo, Leslie Lobel, Stephen Balinandi, Julius J. Lutwama, Larry Zeitlin, Thomas W. Geisbert, Felix A. Rey, Simone Sidoli, Jason S. McLellan, Jonathan R. Lai, Zachary A. Bornholdt, John M. Dye, Laura M. Walker, Kartik Chandran

Issue&Volume: 2021-06-01

Abstract: Crimean-Congo hemorrhagic fever virus (CCHFV) is a World Health Organization prioritypathogen. CCHFV infections cause a highly lethal hemorrhagic fever for which specifictreatments and vaccines are urgently needed. Here, we characterize the human immuneresponse to natural CCHFV infection to identify potent neutralizing monoclonal antibodies(nAbs) targeting the viral glycoprotein. Competition experiments showed that thesenAbs bind six distinct antigenic sites in the Gc subunit. These sites were furtherdelineated through mutagenesis and mapped onto a prefusion model of Gc. Pairwise screeningidentified combinations of non-competing nAbs that afford synergistic neutralization.Further enhancements in neutralization breadth and potency were attained by physicallylinking variable domains of synergistic nAb pairs through bispecific antibody (bsAb)engineering. Although multiple nAbs protected mice from lethal CCHFV challenge inpre- or post-exposure prophylactic settings, only a single bsAb, DVD-121-801, affordedtherapeutic protection. DVD-121-801 is a promising candidate suitable for clinicaldevelopment as a CCHFV therapeutic.

DOI: 10.1016/j.cell.2021.05.001

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00584-5