The emergence of antibody therapies for Ebola
The emergence of antibody therapies for Ebola
复制标题
DOI：
10.3233/hab-150284
复制
发表时间：
2014-01-01
期刊：
影响因子：
--
通讯作者：
Zeitlin, Larry
中科院分区：
文献类型：
--
作者：
Hiatt, Andrew;Pauly, Michael;Zeitlin, Larry
这篇综述描述了导致最近在西非爆发的埃博拉严重疫情的埃博拉单抗的发展历史。埃博拉病毒在开发治疗性抗体策略的长期努力中提出了许多令人困惑的挑战。自1999年首次报道中和人抗埃博拉单抗以来，从体外中和导致体内保护和治疗的直接进展尚未发生。许多单抗，包括第一个报告的单抗，尽管对啮齿动物有保护作用，但未能保护非人类灵长类动物(HAP)。对效应器功能对抗体效力的作用的认识有助于理解体内保护的机制。然而，通过暴露后对NHP的治疗来衡量，一个关键的贡献涉及对mAb鸡尾酒的全面测试。这一努力得到了植物生产技术的帮助，在这种技术中，可以快速生产和测试各种单抗组合。引入适当的修饰，如特定的葡聚糖谱，也提高了治疗效果。由此产生的鸡尾酒ZMapp(TM)由从众多单抗候选中鉴定的三种单抗组成。ZMapp(TM)目前正在人体临床试验中进行评估，但已经在提高人们对埃博拉抗体疗法潜力的认识方面发挥了作用。
This review describes the history of Ebola monoclonal antibody (mAb) development leading up to the recent severe Ebola outbreak in West Africa. The Ebola virus has presented numerous perplexing challenges in the long effort to develop therapeutic antibody strategies. Since the first report of a neutralizing human anti-Ebola mAb in 1999, the straightforward progression from in vitro neutralization resulting in in vivo protection and therapy has not occurred. A number of mAbs, including the first reported, failed to protect non-human primates (NHPs) in spite of protection in rodents. An appreciation of the role of effector functions to antibody efficacy has contributed significantly to understanding mechanisms of in vivo protection. However a crucial contribution, as measured by post-exposure therapy of NHPs, involved the comprehensive testing of mAb cocktails. This effort was aided by the use of plant production technology where various combinations of mAbs could be rapidly produced and tested. Introduction of appropriate modifications, such as specific glycan profiles, also improved therapeutic efficacy. The resulting cocktail, ZMapp (TM), consists of three mAbs that were identified from numerous mAb candidates. ZMapp (TM) is now being evaluated in human clinical trials but has already played a role in bringing awareness to the potential of antibody therapy for Ebola.