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植物生产的新兴和再现传染病及生物恐怖制剂候选对策。

Plant-produced candidate countermeasures against emerging and reemerging infections and bioterror agents.

机构信息

Fraunhofer USA Center for Molecular Biotechnology, Newark, DE, USA.

出版信息

Plant Biotechnol J. 2015 Oct;13(8):1136-59. doi: 10.1111/pbi.12475.

Abstract

Despite progress in the prevention and treatment of infectious diseases, they continue to present a major threat to public health. The frequency of emerging and reemerging infections and the risk of bioterrorism warrant significant efforts towards the development of prophylactic and therapeutic countermeasures. Vaccines are the mainstay of infectious disease prophylaxis. Traditional vaccines, however, are failing to satisfy the global demand because of limited scalability of production systems, long production timelines and product safety concerns. Subunit vaccines are a highly promising alternative to traditional vaccines. Subunit vaccines, as well as monoclonal antibodies and other therapeutic proteins, can be produced in heterologous expression systems based on bacteria, yeast, insect cells or mammalian cells, in shorter times and at higher quantities, and are efficacious and safe. However, current recombinant systems have certain limitations associated with production capacity and cost. Plants are emerging as a promising platform for recombinant protein production due to time and cost efficiency, scalability, lack of harboured mammalian pathogens and possession of the machinery for eukaryotic post-translational protein modification. So far, a variety of subunit vaccines, monoclonal antibodies and therapeutic proteins (antivirals) have been produced in plants as candidate countermeasures against emerging, reemerging and bioterrorism-related infections. Many of these have been extensively evaluated in animal models and some have shown safety and immunogenicity in clinical trials. Here, we overview ongoing efforts to producing such plant-based countermeasures.

摘要

尽管在传染病的预防和治疗方面取得了进展,但它们仍然对公众健康构成重大威胁。新发和再现传染病的频率以及生物恐怖主义的风险,需要我们大力开发预防和治疗对策。疫苗是传染病预防的主要手段。然而,由于生产系统的可扩展性有限、生产时间长以及对产品安全性的担忧,传统疫苗无法满足全球需求。亚单位疫苗是传统疫苗的一种极具前景的替代品。亚单位疫苗以及单克隆抗体和其他治疗性蛋白,可以在基于细菌、酵母、昆虫细胞或哺乳动物细胞的异源表达系统中生产,生产时间更短、产量更高,并且有效且安全。然而,目前的重组系统在生产能力和成本方面存在一定的局限性。由于时间和成本效率高、可扩展性强、缺乏哺乳动物病原体以及拥有真核生物翻译后蛋白修饰的机制,植物正成为重组蛋白生产的有前途的平台。迄今为止,已经有多种亚单位疫苗、单克隆抗体和治疗性蛋白(抗病毒药物)在植物中被生产出来,作为针对新发、再现和生物恐怖主义相关感染的候选对策。其中许多已在动物模型中进行了广泛评估,一些已在临床试验中显示出安全性和免疫原性。在这里,我们概述了正在进行的生产此类基于植物的对策的努力。

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