In vitro and in vivo efficacy of anti-chikungunya virus monoclonal antibodies produced in wild-type and glycoengineered Nicotiana benthamiana plants
In vitro and in vivo efficacy of anti-chikungunya virus monoclonal antibodies produced in wild-type and glycoengineered Nicotiana benthamiana plants
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DOI：
10.1111/pbi.13194
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发表时间：
2020-01-01
影响因子：
13.8
通讯作者：
Chen, Qiang
中科院分区：
文献类型：
--
作者：
Hurtado, Jonathan;Acharya, Dhiraj;Chen, Qiang
基孔肯雅病毒（CHIKV）是一种蚊子传播的甲病毒，其感染可导致人类长期衰弱性关节炎。目前，没有许可的疫苗或治疗剂用于人类对抗CHIKV感染。在这项研究中，我们探索了使用野生型（WT）和糖工程化（Delta XFT）本氏烟草植物中产生的抗CHIKV单克隆抗体（mAb）治疗小鼠模型中的CHIKV感染的可行性。CHIKV mAb在植物叶片中高效表达和组装，并通过简单的纯化方案富集至均一。虽然Delta XFT中产生的mAb在Fc结构域处携带单个N-聚糖物质，即GnGn结构，但WT产生的mAb显示出N-聚糖的混合物，包括典型的植物GnGnXF（3）聚糖，伴有不完全加工的寡糖苷结构。WT和Delta XFT植物产生的mAb均表现出针对CHIKV的有效体外中和活性。值得注意的是，两种mAb糖型在小鼠模型中均显示出体内功效，Delta XFT产生的mAb的功效略微增加。这是植物产生的mAb针对CHIKV的功效的首次报道，其证明了使用植物作为用于产生功能活性CHIKV mAb的有效平台的能力，并且暗示了通过控制Fc糖基化优化体内活性。
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus, and its infection can cause long-term debilitating arthritis in humans. Currently, there are no licensed vaccines or therapeutics for human use to combat CHIKV infections. In this study, we explored the feasibility of using an anti-CHIKV monoclonal antibody (mAb) produced in wild-type (WT) and glycoengineered (Delta XFT) Nicotiana benthamiana plants in treating CHIKV infection in a mouse model. CHIKV mAb was efficiently expressed and assembled in plant leaves and enriched to homogeneity by a simple purification scheme. While mAb produced in Delta XFT carried a single N-glycan species at the Fc domain, namely GnGn structures, WT produced mAb exhibited a mixture of N-glycans including the typical plant GnGnXF(3) glycans, accompanied by incompletely processed and oligomannosidic structures. Both WT and Delta XFT plant-produced mAbs demonstrated potent in vitro neutralization activity against CHIKV. Notably, both mAb glycoforms showed in vivo efficacy in a mouse model, with a slight increased efficacy by the Delta XFT-produced mAbs. This is the first report of the efficacy of plant-produced mAbs against CHIKV, which demonstrates the ability of using plants as an effective platform for production of functionally active CHIKV mAbs and implies optimization of in vivo activity by controlling Fc glycosylation.