The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA.
Department of Cell and Molecular Biology, University of Southern Mississippi, Hattiesburg, MS, USA.
Plant Biotechnol J. 2020 Jan;18(1):266-273. doi: 10.1111/pbi.13194. Epub 2019 Jun 26.
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 (∆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 ∆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 glycans, accompanied by incompletely processed and oligomannosidic structures. Both WT and ∆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 ∆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.
基孔肯雅病毒（CHIKV）是一种经蚊子传播的甲病毒，其感染可导致人类长期出现使人虚弱的关节炎。目前，尚无针对 CHIKV 感染的人类使用的许可疫苗或疗法。在这项研究中，我们探索了使用在野生型（WT）和糖基工程化（∆XFT）烟草原生质体中产生的抗 CHIKV 单克隆抗体（mAb）在小鼠模型中治疗 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到均一性。虽然在 ∆XFT 中产生的 mAb 在 Fc 结构域带有单一的 N-聚糖，即 GnGn 结构，但 WT 产生的 mAb 表现出 N-聚糖的混合物，包括典型的植物 GnGnXF 聚糖，同时伴有不完全加工和寡甘露糖结构。WT 和 ∆XFT 植物产生的 mAb 均显示出针对 CHIKV 的强大体外中和活性。值得注意的是，两种 mAb 糖型在小鼠模型中均显示出体内疗效，∆XFT 产生的 mAb 略有增加。这是首次报道植物产生的 mAb 对 CHIKV 的疗效，证明了使用植物作为生产功能活性 CHIKV mAb 的有效平台的能力，并暗示通过控制 Fc 糖基化优化体内活性。
