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在植物中生产基于血凝素的病毒样颗粒:应对大流行性流感的快速、有效和安全的反应。

The production of hemagglutinin-based virus-like particles in plants: a rapid, efficient and safe response to pandemic influenza.

机构信息

Medicago Inc., Bureau, QC, Canada.

出版信息

Plant Biotechnol J. 2010 Jun;8(5):607-19. doi: 10.1111/j.1467-7652.2009.00496.x. Epub 2010 Feb 18.

Abstract

During the last decade, the spectre of an influenza pandemic of avian origin has led to a revision of national and global pandemic preparedness plans and has stressed the need for more efficient influenza vaccines and manufacturing practices. The 2009 A/H1N1 (swine flu) outbreak has further emphasized the necessity to develop new solutions for pandemic influenza vaccines. Influenza virus-like particles (VLPs)-non-infectious particles resembling the influenza virus-represent a promising alternative to inactivated and split-influenza virions as antigens, and they have shown uniqueness by inducing a potent immune response through both humoral and cellular components of the immune system. Our group has developed a plant-based transient influenza VLP manufacturing platform capable of producing influenza VLPs with unprecedented speed. Influenza VLP expression and purification technologies were brought to large-scale production of GMP-grade material, and pre-clinical studies have demonstrated that low doses of purified, plant-produced influenza VLPs induce a strong and broad immune response in mice and ferrets. This review positions the recent developments towards the successful production of influenza VLPs in plants, including the production of VLPs from other human viruses and other forms of influenza antigens. The platform developed for large-scale production of VLPs is also presented along with an assessment of the speed of the platform to produce the first experimental vaccine lots from the identification of a new influenza strain.

摘要

在过去的十年中,禽流感大流行的幽灵导致了国家和全球大流行防范计划的修订,并强调了需要更有效的流感疫苗和制造方法。2009 年 A/H1N1(猪流感)爆发进一步强调了需要为大流行性流感疫苗开发新的解决方案。流感病毒样颗粒(VLPs)是非传染性颗粒,类似于流感病毒,作为抗原代表了一种很有前途的替代灭活和分裂流感病毒的方法,它们通过诱导体液和细胞免疫成分的强大免疫反应而具有独特性。我们的小组开发了一种基于植物的瞬时流感 VLPs 制造平台,能够以空前的速度生产流感 VLPs。流感 VLP 的表达和纯化技术已被应用于大规模生产 GMP 级别的材料,临床前研究表明,低剂量的纯化、植物生产的流感 VLPs 可在小鼠和雪貂中诱导强烈而广泛的免疫反应。本文综述了在植物中成功生产流感 VLPs 的最新进展,包括从其他人类病毒和其他形式的流感抗原生产 VLPs。还介绍了用于大规模生产 VLPs 的平台,以及从新流感株的鉴定到生产第一批实验疫苗的速度评估。

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