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      Plant‐made vaccines for humans and animals

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          Summary

          The concept of using plants to produce high‐value pharmaceuticals such as vaccines is 20 years old this year and is only now on the brink of realisation as an established technology. The original reliance on transgenic plants has largely given way to transient expression; proofs of concept for human and animal vaccines and of efficacy for animal vaccines have been established; several plant‐produced vaccines have been through Phase I clinical trials in humans and more are scheduled; regulatory requirements are more clear than ever, and more facilities exist for manufacture of clinic‐grade materials. The original concept of cheap edible vaccines has given way to a realisation that formulated products are required, which may well be injectable. The technology has proven its worth as a means of cheap, easily scalable production of materials: it now needs to find its niche in competition with established technologies. The realised achievements in the field as well as promising new developments will be reviewed, such as rapid‐response vaccines for emerging viruses with pandemic potential and bioterror agents.

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          Most cited references147

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

          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.
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            Magnifection--a new platform for expressing recombinant vaccines in plants.

            Today, plant biotechnology relies on two processes for delivery and expression of heterologous genes in plants: stable genetic transformation and transient infection with viral vectors. Although much faster, the transient route until recently was limited because of virus' low infectivity and its inability to carry average-size or larger transgenes. A recently developed new generation transfection technology overcomes these limitations by relying on Agrobacterium as an infective systemic agent that delivers viral replicons. This improved process is being used to simultaneously start transient gene amplification and high-level expression in all mature leaves of a plant, and such a transfection can be done on an industrial scale. This eclectic technology, called 'magnifection', combines advantages of three biological systems: vector efficiency and efficient systemic DNA delivery of Agrobacterium, speed and expression level/yield of a plant RNA virus, as well as posttranslational capabilities and low production costs of a plant. The proposed process allows for industrial production that does not require genetic modification of plants, that is much faster than previous methods, and that is biologically safe. Numerous applications in the area of vaccine manufacturing are being discussed.
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              Plant-specific glycosylation patterns in the context of therapeutic protein production.

              While N-glycan synthesis in the endoplasmic reticulum (ER) is relatively well conserved in eukaryotes, N-glycan processing and O-glycan biosynthesis in the Golgi apparatus are kingdom specific and result in different oligosaccharide structures attached to glycoproteins in plants and mammals. With the prospect of using plants as alternative hosts to mammalian cell lines for the production of therapeutic glycoproteins, significant progress has been made towards the humanization of protein N-glycosylation in plant cells. To date, successful efforts in this direction have mainly focused on the targeted expression of therapeutic proteins, the knockout of plant-specific N-glycan-processing genes, and/or the introduction of the enzymatic machinery catalyzing the synthesis, transport and addition of human sugars. By contrast, very little attention has been paid until now to the O-glycosylation status of plant-made therapeutic proteins, which is surprising considering that hundreds of human proteins represent good candidates for Hyp-O glycosylation when produced in a plant expression system. This review describes protein N- and O-linked glycosylation in plants and highlights the limitations and advantages of plant-specific glycosylation on plant-made biopharmaceuticals.

                Author and article information

                Journal
                Plant Biotechnol J
                Plant Biotechnol. J
                10.1111/(ISSN)1467-7652
                PBI
                Plant Biotechnology Journal
                Blackwell Publishing Ltd (Oxford, UK )
                1467-7644
                1467-7652
                11 March 2010
                June 2010
                : 8
                : 5 , Success Stories in Molecular Farming ( doiID: 10.1111/pbi.2010.8.issue-5 )
                : 620-637
                Affiliations
                [ 1 ]Department of Molecular and Cell Biology, University of Cape Town, Private Bag, Rondebosch, South Africa
                [ 2 ]Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa
                Author notes
                [*] [* ] Correspondence (fax +27 0 21 650 2646; email ed.rybicki@ 123456uct.ac.za )
                Article
                PBI507
                10.1111/j.1467-7652.2010.00507.x
                7167690
                20233333
                1181e9a2-6d6c-4ca4-8c9b-df170d526094
                © 2010 The Author. Journal compilation © 2010 Blackwell Publishing Ltd

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 10 September 2009
                : 30 November 2009
                : 2 December 2009
                Page count
                Figures: 1, Tables: 0, Pages: 18
                Categories
                Review Articles
                Custom metadata
                2.0
                June 2010
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020

                Biotechnology
                vaccine,plant,transgenic plant,transient expression,plant biotechnology,pharmaceutical
                Biotechnology
                vaccine, plant, transgenic plant, transient expression, plant biotechnology, pharmaceutical

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