Bioprocessing of plant-derived virus-like particles of Norwalk virus capsid protein under current Good Manufacture Practice regulations.
Bioprocessing of plant-derived virus-like particles of Norwalk virus capsid protein under current Good Manufacture Practice regulations.
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DOI：
10.1007/s00299-011-1196-6
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发表时间：
2012-03
影响因子：
6.2
通讯作者：
Chen, Qiang
中科院分区：
文献类型：
--
作者：
Lai, Huafang;Chen, Qiang
尽管在植物中成功表达了多种亚单位疫苗蛋白，并且最近通过瞬时表达系统在提高疫苗积累水平方面取得了进展，但仍然没有植物来源的疫苗被许可用于人类使用。植物制造疫苗缺乏商业成功在于仍需克服的几个技术和监管障碍。这些挑战包括缺乏可扩展的下游加工程序，生产工艺合规性的不确定性，以及缺乏符合监管机构在身份，纯度，效力和安全性方面所需标准的植物衍生产品的证明。在这项研究中，我们解决了这些剩余的挑战，并成功地证明了使用植物生产药物级诺瓦克病毒（NV）疫苗的能力，根据目前的良好生产规范（cGMP）的指导方针，在多个克规模。我们的研究结果表明，一个有效的和可扩展的提取和纯化方案可以建立处理NV衣壳蛋白（NVCP）的病毒样颗粒（VLP）。我们在cGMP法规下成功运营了NVCP的上下游生产流程。此外，植物来源的NVCP VLP证明了符合预设放行质量标准的同一性、纯度、效价和安全性。该材料正在I期人体临床试验中进行测试。这项研究提供了在学术环境中根据cGMP法规大规模生产植物源疫苗的第一份报告，也是植物生产疫苗成为商业现实的重要一步。
Despite the success in expressing a variety of subunit vaccine proteins in plants and the recent stride in improving vaccine accumulation levels by transient expression systems, there is still no plant-derived vaccine that has been licensed for human use. The lack of commercial success of plant-made vaccines lies in several technical and regulatory barriers that remain to be overcome. These challenges include the lack of scalable downstream processing procedures, the uncertainty of regulatory compliance of production processes, and the lack of demonstration of plant-derived products that meet the required standards of regulatory agencies in identity, purity, potency and safety. In this study, we addressed these remaining challenges and successfully demonstrate the ability of using plants to produce a pharmaceutical grade Norwalk virus (NV) vaccine under current Good Manufacture Practice (cGMP) guidelines at multiple gram scales. Our results demonstrate that an efficient and scalable extraction and purification scheme can established for processing virus-like particles (VLP) of NV capsid protein (NVCP). We successfully operated the upstream and downstream NVCP production processes under cGMP regulations. Furthermore, plant-derived NVCP VLP demonstrates the identity, purity, potency and safety that meet the preset release specifications. This material is being tested in a Phase I human clinical trial. This research provides the first report of producing a plant-derived vaccine at scale under cGMP regulations in an academic setting and an important step for plant-produced vaccines to become a commercial reality.
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影响因子：
46.9
作者：
Thiel, KA
通讯作者：
Thiel, KA
影响因子：
--
作者：
Velasquez, Lissette S.;Hjelm, Brooke E.;Herbst-Kralovetz, Melissa M.
通讯作者：
Herbst-Kralovetz, Melissa M.
影响因子：
56.9
作者：
Prasad, BVV;Hardy, ME;Estes, MK
通讯作者：
Estes, MK
DOI：
10.1073/pnas.0606631103
发表时间：
2006-10-03
影响因子：
11.1
作者：
Giritch, Anatoli;Marillonnet, Sylvestre;Gleba, Yuri
通讯作者：
Gleba, Yuri
影响因子：
11.8
作者：
Patel, Manish M.;Widdowson, Marc-Alain;Glass, Roger I.;Akazawa, Kenichiro;Vinje, Jan;Parashar, Umesh D.
通讯作者：
Parashar, Umesh D.