A plant-based system for rapid production of influenza vaccine antigens

Fraunhofer USA Center for Molecular Biotechnology, Newark, DE 19711, USA.
Influenza and Other Respiratory Viruses (Impact Factor: 2.2). 10/2011; 6(3):204-10. DOI: 10.1111/j.1750-2659.2011.00295.x
Source: PubMed


Influenza virus is a globally important respiratory pathogen that causes a high degree of annual morbidity and mortality. Significant antigenic drift results in emergence of new, potentially pandemic, virus variants. The best prophylactic option for controlling emerging virus strains is to manufacture and administer pandemic vaccines in sufficient quantities and to do so in a timely manner without impacting the regular seasonal influenza vaccine capacity. Current, egg-based, influenza vaccine production is well established and provides an effective product, but has limited capacity and speed.
To satisfy the additional global demand for emerging influenza vaccines, high-performance cost-effective technologies need to be developed. Plants have a potential as an economic and efficient large-scale production platform for vaccine antigens.
In this study, a plant virus-based transient expression system was used to produce hemagglutinin (HA) proteins from the three vaccine strains used during the 2008-2009 influenza season, A/Brisbane/59/07 (H1N1), A/Brisbane/10/07 (H3N2), and B/Florida/4/06, as well as from the recently emerged novel H1N1 influenza A virus, A/California/04/09.
The recombinant plant-based HA proteins were engineered and produced in Nicotiana benthamiana plants within 2 months of obtaining the genetic sequences specific to each virus strain. These antigens expressed at the rate of 400-1300 mg/kg of fresh leaf tissue, with >70% solubility. Immunization of mice with these HA antigens induced serum anti-HA IgG and hemagglutination inhibition antibody responses at the levels considered protective against these virus infections.
These results demonstrate the feasibility of our transient plant expression system for the rapid production of influenza vaccine antigens.

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Available from: Brian J Green, Jan 21, 2014
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    • "Similar experiments were done with HAs from the strains comprising the 2008–2009 seasonal vaccine (A/Brisbane/10/07, A/Brisbane/59/07 and B/Flori- da/04/06) and California/04/09 (H1N1) (Shoji et al., 2012 "
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    ABSTRACT: Many examples of a successful application of plant-based expression systems for production of biologically active recombinant proteins exist in the literature. These systems can function as inexpensive platforms for the large scale production of recombinant pharmaceuticals or subunit vaccines. Hemagglutinin (HA) is a major surface antigen of the influenza virus, thus it is in the centre of interests of various subunit vaccine engineering programs. Large scale production of recombinant HA in traditional expression systems, such as mammalian or insect cells, besides other limitations, is expensive and time-consuming. These difficulties stimulate an ever-increasing interest in plant-based production of this recombinant protein. Over the last few years many successful cases of HA production in plants, using both transient and stable expression systems have been reported. Various forms of recombinant HA, including monomers, trimers, virus like particles (VLPs) or chimeric proteins containing its fusion with other polypeptides were obtained and shown to maintain a proper antigenicity. Immunizations of animals (mice, ferrets, rabbits or chickens) with some of these plant-derived hemagglutinin variants were performed, and their effectiveness in induction of immunological response and protection against lethal challenge with influenza virus demonstrated. Plant-produced recombinant subunit vaccines and plant-made VLPs were successfully tested in clinical trials (Phase I and II) that confirmed their tolerance and immunogenicity.
    Full-text · Article · Sep 2014 · Acta biochimica Polonica
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    • "Induced serum anti-HA IgG in test mice, at levels considered protective as estimated by hemagglutination inhibition Shoji et al. 2012 A/ "

    Full-text · Chapter · Jun 2014
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    • "An effective vaccine needs to be produced quickly after strain identification in order to halt the spread of the new strain. NVLPs produced by transient expression address these issues, allowing the rapid and affordable production of strain-specific vaccines in a timely manner and in relevant locations, including the developing world [54, 55, 59, 110]. However, it should also be borne in mind that plants offer advantages for small-scale expression. "
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    ABSTRACT: In recent years, the production of recombinant pharmaceutical proteins in heterologous systems has increased significantly. Most applications involve complex proteins and glycoproteins that are difficult to produce, thus promoting the development and improvement of a wide range of production platforms. No individual system is optimal for the production of all recombinant proteins, so the diversity of platforms based on plants offers a significant advantage. Here, we discuss the production of four recombinant pharmaceutical proteins using different platforms, highlighting from these examples the unique advantages of plant-based systems over traditional fermenter-based expression platforms.
    Full-text · Article · Mar 2014
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