美国范德比尔特大学医学中心James E. Crowe Jr.课题组揭示人类抗体预防东部马脑炎病毒感染的分子机制。相关论文于2020年12月9日在线发表在《细胞》杂志上。

研究人员表征了从东部马脑炎病毒（EEEV）感染的幸存者中分离出来的人单克隆抗体（mAb），其具有有效的EEEV抑制活性（<20 pM）。两种高效中和单克隆抗体EEEV-33和EEEV-143分别与嵌合Sindbis/EEEV病毒体结合的冷冻电镜结构被解析，分辨率分别达到7.2Å和8.3Å。mAb识别两个不同的抗原位点，这些位点对于抑制病毒进入细胞至关重要。EEEV-33和EEEV-143可防止高致病性EEEV对小鼠产生的致命性气溶胶感染。

这些研究为人类中和抗体对EEEV的响应提供了分子基础的见解，并可以促进疫苗和候选抗体治疗剂的开发。

据介绍，EEEV是北美地方性最强的病毒之一。目前没有可用于对抗这种感染的疫苗或抗病毒疗法，并且最近这种感染在人类病例中呈上升趋势。

附：英文原文

Title: Human Antibodies Protect against Aerosolized Eastern Equine Encephalitis Virus Infection

Author: Lauren E. Williamson, Theron Gilliland, Pramod K. Yadav, Elad Binshtein, Robin Bombardi, Nurgun Kose, Rachel S. Nargi, Rachel E. Sutton, Clarissa L. Durie, Erica Armstrong, Robert H. Carnahan, Lauren M. Walker, Arthur S. Kim, Julie M. Fox, Michael S. Diamond, Melanie D. Ohi, William B. Klimstra, James E. Crowe

Issue&Volume: 2020-12-09

Abstract: Eastern equine encephalitis virus (EEEV) is one of the most virulent viruses endemicto North America. No licensed vaccines or antiviral therapeutics are available tocombat this infection, which has recently shown an increase in human cases. Here,we characterize human monoclonal antibodies (mAbs) isolated from a survivor of naturalEEEV infection with potent (<20 pM) inhibitory activity of EEEV. Cryo-electron microscopyreconstructions of two highly neutralizing mAbs, EEEV-33 and EEEV-143, were solvedin complex with chimeric Sindbis/EEEV virions to 7.2 and 8.3 , respectively. ThemAbs recognize two distinct antigenic sites that are critical for inhibiting viralentry into cells. EEEV-33 and EEEV-143 protect against disease following stringentlethal aerosol challenge of mice with highly pathogenic EEEV. These studies provideinsight into the molecular basis for the neutralizing human antibody response againstEEEV and can facilitate development of vaccines and candidate antibody therapeutics.

DOI: 10.1016/j.cell.2020.11.011

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31528-2