Clinical development of plant-produced recombinant pharmaceuticals: Vaccines, antibodies and beyond-猫眼课题宝

植物生产的重组药物的临床开发：疫苗、抗体等

DOI：

发表时间：

2011

期刊：

Human Vaccines

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

V. Yusibov;S. Streatfield;N. Kushnir

在过去的几年里，植物已经成为一个越来越有吸引力的重组蛋白生产平台。这是建立在20年的研究基础上的，从开发口服疫苗的转基因方法开始，其中抗原或疗法可以在加工过的植物生物质中递送，并发展到瞬时表达方法，即通过肠外给药获得高产量的纯化靶标。基于植物的表达系统的优势包括高可扩展性，低上游成本，生物控制，缺乏人类或动物病原体，以及能够产生具有所需结构和生物学功能的靶蛋白。利用转基因和瞬时表达在整个植物或植物细胞培养中，多种重组亚单位候选疫苗、治疗蛋白（包括单克隆抗体）和膳食蛋白已被生产出来。其中一些产品已经在早期临床试验中进行了测试，并显示出安全性和有效性。其中包括腹泻病、乙型肝炎和狂犬病的粘膜疫苗；非霍奇金淋巴瘤、H1N1和H5N1型甲型流感病毒毒株以及家禽新城疫的注射疫苗；以及治疗龋齿和艾滋病毒的局部抗体。随着主要植物性产品进入临床试验，越来越重视按照现行的良好生产规范（cGMP）指南进行生产，以及准备和向相关政府机构提交监管包。

In the last few years, plants have become an increasingly attractive platform for recombinant protein production. This builds on two decades of research, starting with transgenic approaches to develop oral vaccines in which antigens or therapeutics can be delivered in processed plant biomass, and progressing to transient expression approaches whereby high yields of purified targets are administered parenterally. The advantages of plant-based expression systems include high scalability, low upstream costs, biocontainment, lack of human or animal pathogens, and ability to produce target proteins with desired structures and biological functions. Using transgenic and transient expression in whole plants or plant cell culture, a variety of recombinant subunit vaccine candidates, therapeutic proteins, including monoclonal antibodies, and dietary proteins have been produced. Some of these products have been tested in early phase clinical trials, and show safety and efficacy. Among those are mucosal vaccines for diarrheal diseases, hepatitis B and rabies; injectable vaccines for non-Hodgkin’s lymphoma, H1N1 and H5N1 strains of influenza A virus, and Newcastle disease in poultry; and topical antibodies for the treatment of dental caries and HIV. As lead plant-based products have entered clinical trials, there has been increased emphasis on manufacturing under current Good Manufacturing Practice (cGMP) guidelines, and the preparation and presentation to the relevant government agencies of regulatory packages.