The Biodesign Institute, School of Life Sciences, Arizona State University, 1001 S. McAllister Avenue, Tempe, AZ 85287, USA.
Int J Mol Sci. 2017 Dec 25;19(1):54. doi: 10.3390/ijms19010054.
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.
最近寨卡病毒（ZIKV）的爆发突显了开发针对黄病毒（flaviviruses）有效干预措施的迫切需要，许多黄病毒在全球范围内引发了毁灭性的流行。由于单克隆抗体（mAb）的特异性和效力，它们一直处于癌症和许多其他疾病治疗的前沿。尽管哺乳动物细胞产生的 mAb 已显示出作为几种黄病毒治疗候选物的潜力，但它们最终获得人类应用仍面临着一些挑战，包括它们通过抗体依赖性增强（ADE）使接受治疗的患者更容易受到异源黄病毒更严重二次感染的潜在风险。在哺乳动物细胞培养物中生产 mAb 的高成本也给这些药物在发展中国家的可行应用带来了挑战，而大多数黄病毒感染都发生在这些国家。在这里，我们回顾了针对各种黄病毒（包括西尼罗河病毒（WNV）、登革热病毒（DENV）和 ZIKV）的当前治疗性 mAb 候选物。在讨论针对黄病毒表达、表征、下游处理、中和和体内疗效的 mAb 治疗时，我们讨论了利用植物开发更安全、更经济的 mAb 治疗方法的进展。利用植物糖基工程解决 ADE（黄病毒治疗开发的主要障碍）的进展也得到了强调。这些进展表明，植物系统是解决黄病毒 mAb 治疗开发剩余挑战的绝佳选择，并可能促进这些药物候选物的最终商业化。
