Jugler Collin, Sun Haiyan, Grill Francisca, Kibler Karen, Esqueda Adrian, Lai Huafang, Li Yize, Lake Douglas, Chen Qiang
The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
Vaccines (Basel). 2022 May 12;10(5):772. doi: 10.3390/vaccines10050772.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a public health crisis over the last two years. Monoclonal antibody (mAb)-based therapeutics against the spike (S) protein have been shown to be effective treatments for SARS-CoV-2 infection, especially the original viral strain. However, the current mAbs produced in mammalian cells are expensive and might be unaffordable for many. Furthermore, the emergence of variants of concern demands the development of strategies to prevent mutant escape from mAb treatment. Using a cocktail of mAbs that bind to complementary neutralizing epitopes is one such strategy. In this study, we use plants in an effort to expedite the development of efficacious and affordable antibody cocktails against SARS-CoV-2. We show that two mAbs can be highly expressed in plants and are correctly assembled into IgG molecules. Moreover, they retain target epitope recognition and, more importantly, neutralize multiple SARS-CoV-2 variants. We also show that one plant-made mAb has neutralizing synergy with other mAbs that we developed in hybridomas. This is the first report of a plant-made mAb to be assessed as a potential component of a SARS-CoV-2 neutralizing cocktail. This work may offer a strategy for using plants to quickly develop mAb cocktail-based therapeutics against emerging viral diseases with high efficacy and low costs.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在过去两年中引发了一场公共卫生危机。基于单克隆抗体（mAb）的针对刺突（S）蛋白的疗法已被证明是治疗SARS-CoV-2感染的有效方法，尤其是针对原始病毒株。然而，目前在哺乳动物细胞中生产的单克隆抗体价格昂贵，许多人可能无法承受。此外，值得关注的变异株的出现需要制定策略来防止突变体逃脱单克隆抗体治疗。使用结合互补中和表位的单克隆抗体混合物就是这样一种策略。在本研究中，我们利用植物来加速开发针对SARS-CoV-2的有效且经济实惠的抗体混合物。我们表明，两种单克隆抗体可以在植物中高度表达，并正确组装成IgG分子。此外，它们保留了对靶表位的识别能力，更重要的是，能中和多种SARS-CoV-2变异株。我们还表明，一种植物源单克隆抗体与我们在杂交瘤中开发的其他单克隆抗体具有中和协同作用。这是关于将植物源单克隆抗体评估为SARS-CoV-2中和混合物潜在成分的首次报道。这项工作可能为利用植物快速开发基于单克隆抗体混合物的高效低成本治疗新兴病毒性疾病的策略提供思路。
