Plant-derived single domain COVID-19 antibodies.
Plant-derived single domain COVID-19 antibodies.
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DOI：
10.1016/j.jconrel.2023.05.030
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发表时间：
2023-07
期刊：
影响因子：
--
通讯作者：
Minko T
中科院分区：
文献类型：
--
作者：
Shen AM;Malekshah OM;Pogrebnyak N;Minko T
数据显示，COVID-19导致住院和死亡的风险有所降低。到目前为止，全球SARS-CoV-2疫苗接种正在进行中，但迫切需要额外的治疗方法来预防和治愈未接种过疫苗甚至接种过疫苗的人的感染。中和性单克隆抗体在SARS-CoV-2感染的预防和治疗中具有重要的应用前景。然而，传统的大规模生产这种抗体的方法是缓慢的，极其昂贵的，并且具有被病毒、朊病毒、致癌DNA和其他污染物污染的高风险。本研究旨在开发一种在植物系统中生产抗SARS-CoV-2刺突蛋白（S）的单克隆抗体（mAb）的方法，该方法具有独特的优势，例如缺乏人和动物病原体或细菌毒素，相对低的生产成本，以及易于放大生产。我们选择了一个单一的N-末端结构域功能骆驼源重（H）链抗体片段（VHH，AKA纳米抗体）靶向的受体结合结构域的SARS-CoV-2刺突蛋白，并开发了他们的快速生产方法使用转基因植物和植物细胞悬浮液。将分离和纯化的植物来源的VHH抗体与在传统哺乳动物和细菌表达系统中产生的mAb进行比较。发现使用所提出的转化和纯化方法的植物产生的VHH具有与来自细菌和哺乳动物细胞培养物的单克隆抗体相当的结合SARS-CoV-2刺突蛋白的能力。本研究的结果证实了与传统方法相比，在相对较短的时间跨度内以较低的成本在植物系统中生产具有高结合靶向COVID-19刺突蛋白能力的单克隆单链抗体的可见性。此外，类似的植物生物技术方法可用于生产针对其他类型病毒的单克隆中和抗体。
Data show a decrease in the risk of hospitalization and death from COVID-19. To date, global vaccinations for SARS-CoV-2 protections are underway, but additional treatments are urgently needed to prevent and cure infection among naïve and even vaccinated people. Neutralizing monoclonal antibodies are very promising for prophylaxis and therapy of SARS-CoV-2 infections. However, traditional large-scale methods of producing such antibodies are slow, extremely expensive and possess a high risk of contamination with viruses, prions, oncogenic DNA and other pollutants. The present study is aimed at developing an approach of producing monoclonal antibodies (mAbs) against SARS-CoV-2 spike (S) protein in plant systems which offers unique advantages, such as the lack of human and animal pathogens or bacterial toxins, relatively low-cost manufacturing, and ease of production scale-up. We selected a single N-terminal domain functional camelid-derived heavy (H)-chain antibody fragments (VHH, AKA nanobodies) targeted to receptor binding domain of SARS-CoV-2 spike protein and developed methods of their rapid production using transgenic plants and plant cell suspensions. Isolated and purified plant-derived VHH antibodies were compared with mAbs produced in traditional mammalian and bacterial expression systems. It was found that plant generated VHH using the proposed methods of transformation and purification possess the ability to bind to SARS-CoV-2 spike protein comparable to that of monoclonal antibodies derived from bacterial and mammalian cell cultures. The results of the present studies confirm the visibility of producing monoclonal single-chain antibodies with a high ability to bind the targeted COVID-19 spike protein in plant systems within a relatively shorter time span and at a lower cost when compared with traditional methods. Moreover, similar plant biotechnology approaches can be used for producing monoclonal neutralizing antibodies against other types of viruses.
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影响因子：
3.6
作者：
Freise AC;Wu AM
通讯作者：
Wu AM
影响因子：
5.2
作者：
Pogrebnyak N;Markley K;Smirnov Y;Brodzik R;Bandurska K;Koprowski H;Golovkin M
通讯作者：
Golovkin M
DOI：
10.3791/253
发表时间：
2007-01-01
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Froger, Alexandrine;Hall, James E
通讯作者：
Hall, James E
影响因子：
--
作者：
Hiatt, Andrew;Pauly, Michael;Zeitlin, Larry
通讯作者：
Zeitlin, Larry
影响因子：
6.8
作者：
Koenning, Doreen;Zielonka', Stefan;Kolmarl, Harald
通讯作者：
Kolmarl, Harald