Development of Antibody Therapeutics against Flaviviruses.
Development of Antibody Therapeutics against Flaviviruses.
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DOI：
10.3390/ijms19010054
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发表时间：
2017-12-25
影响因子：
5.6
通讯作者：
Lai H
中科院分区：
文献类型：
--
作者：
Sun H;Chen Q;Lai H
最近寨卡病毒(ZIKV)的暴发突显了迫切需要开发有效的干预措施来抗击黄病毒，其中许多黄病毒在世界各地造成毁灭性的流行病。由于其特异性和效力，单抗一直处于癌症和其他一系列疾病治疗的前沿。虽然哺乳动物细胞产生的单抗已经显示出对几种黄病毒的治疗候选前景，但它们最终被批准用于人类仍然面临着几个挑战，包括它们通过抗体依赖增强(ADE)使接受治疗的患者容易受到异源黄病毒更严重的继发感染的潜在风险。在哺乳动物细胞培养中生产单抗的高成本也对这些药物在大多数黄病毒感染发生的发展中国家的可行应用构成了挑战。在这里，我们综述了目前针对包括西尼罗河病毒(WNV)、登革病毒(DENV)和寨卡病毒(ZIKV)在内的各种黄病毒的治疗性mAb候选。从植物的表达、特性、下游加工、中和作用和体内疗效等方面讨论了利用植物开发更安全、更经济的抗黄病毒单抗治疗药物的进展。强调了利用植物糖工程来解决ADE的进展，ADE是黄病毒治疗发展的主要障碍。这些进展表明，以植物为基础的系统是解决针对黄病毒的单抗治疗开发的剩余挑战的极佳替代方案，并可能促进这些候选药物的最终商业化。
Recent outbreaks of Zika virus (ZIKV) highlight the urgent need to develop efficacious interventions against flaviviruses, many of which cause devastating epidemics around the world. Monoclonal antibodies (mAb) have been at the forefront of treatment for cancer and a wide array of other diseases due to their specificity and potency. While mammalian cell-produced mAbs have shown promise as therapeutic candidates against several flaviviruses, their eventual approval for human application still faces several challenges including their potential risk of predisposing treated patients to more severe secondary infection by a heterologous flavivirus through antibody-dependent enhancement (ADE). The high cost associated with mAb production in mammalian cell cultures also poses a challenge for the feasible application of these drugs to the developing world where the majority of flavivirus infection occurs. Here, we review the current therapeutic mAb candidates against various flaviviruses including West Nile (WNV), Dengue virus (DENV), and ZIKV. The progress of using plants for developing safer and more economical mAb therapeutics against flaviviruses is discussed within the context of their expression, characterization, downstream processing, neutralization, and in vivo efficacy. The progress of using plant glycoengineering to address ADE, the major impediment of flavivirus therapeutic development, is highlighted. These advancements suggest that plant-based systems are excellent alternatives for addressing the remaining challenges of mAb therapeutic development against flavivirus and may facilitate the eventual commercialization of these drug candidates.
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影响因子：
6.7
作者：
Balsitis SJ;Williams KL;Lachica R;Flores D;Kyle JL;Mehlhop E;Johnson S;Diamond MS;Beatty PR;Harris E
通讯作者：
Harris E
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6.7
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通讯作者：
Sallusto F
影响因子：
3.2
作者：
Calzolari, Mattia;Ze-Ze, Libia;Dottori, Michele
通讯作者：
Dottori, Michele