Preclinical and Clinical Development of Plant-Made Virus-Like Particle Vaccine against Avian H5N1 Influenza

Landry, Nathalie; Ward, Brian J.; Trépanier, Sonia; Montomoli, Emanuele; Dargis, Michèle; Lapini, Giulia; Vézina, Louis‐P.

doi:10.1371/journal.pone.0015559

Cited by 261 publications

(235 citation statements)

References 23 publications

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“…Manufacturing processes based on transient expression of proteins in plants and similar to those described in this report have already been brought into FDA Good Manufacturing Practice (GMP) compliance, and several biopharmaceuticals produced transiently in plants are currently undergoing clinical studies (26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

Broad and efficient control of major foodborne pathogenic strains of Escherichia coli by mixtures of plant-produced colicins

Schulz

Stephan

Hahn

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Enterohemorrhagic Escherichia coli (EHEC) is one of the leading causes of bacterial enteric infections worldwide, causing ∼100,000 illnesses, 3,000 hospitalizations, and 90 deaths annually in the United States alone. These illnesses have been linked to consumption of contaminated animal products and vegetables. Currently, other than thermal inactivation, there are no effective methods to eliminate pathogenic bacteria in food. Colicins are nonantibiotic antimicrobial proteins, produced by E. coli strains that kill or inhibit the growth of other E. coli strains. Several colicins are highly effective against key EHEC strains. Here we demonstrate very high levels of colicin expression (up to 3 g/kg of fresh biomass) in tobacco and edible plants (spinach and leafy beets) at costs that will allow commercialization. Among the colicins examined, plant-expressed colicin M had the broadest antimicrobial activity against EHEC and complemented the potency of other colicins. A mixture of colicin M and colicin E7 showed very high activity against all major EHEC strains, as defined by the US Department of Agriculture/Food and Drug Administration. Treatments with low (less than 10 mg colicins per L) concentrations reduced the pathogenic bacterial load in broth culture by 2 to over 6 logs depending on the strain. In experiments using meats spiked with E. coli O157:H7, colicins efficiently reduced the population of the pathogen by at least 2 logs. Plant-produced colicins could be effectively used for the broad control of pathogenic E. coli in both plant-and animal-based food products and, in the United States, colicins could be approved using the generally recognized as safe (GRAS) regulatory approval pathway.antimicrobials | colicin | EHEC | food safety | plant-made recombinant proteins

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Section: Discussionmentioning

confidence: 99%

Broad and efficient control of major foodborne pathogenic strains of Escherichia coli by mixtures of plant-produced colicins

Schulz

Stephan

Hahn

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Plant-based systems for the expression of biopharmaceuticals have shown promise in recent years as several novel treatments for diseases, like Gaucher's Disease 2 , and avian H5N1 influenza 3 , have shown success in clinical trials. The development of competent mechanisms for recombinant protein expression in plants in the decades since those initial experiments has created the potential for plant-based systems to alter the current paradigm of protein production for three primary reasons.…”

Section: Introductionmentioning

confidence: 99%

Efficient Agroinfiltration of Plants for High-level Transient Expression of Recombinant Proteins

Leuzinger

Dent

Hurtado

et al. 2013

JoVE

155

157

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Mammalian cell culture is the major platform for commercial production of human vaccines and therapeutic proteins. However, it cannot meet the increasing worldwide demand for pharmaceuticals due to its limited scalability and high cost. Plants have shown to be one of the most promising alternative pharmaceutical production platforms that are robust, scalable, low-cost and safe. The recent development of virus-based vectors has allowed rapid and high-level transient expression of recombinant proteins in plants. To further optimize the utility of the transient expression system, we demonstrate a simple, efficient and scalable methodology to introduce target-gene containing Agrobacterium into plant tissue in this study. Our results indicate that agroinfiltration with both syringe and vacuum methods have resulted in the efficient introduction of Agrobacterium into leaves and robust production of two fluorescent proteins; GFP and DsRed. Furthermore, we demonstrate the unique advantages offered by both methods. Syringe infiltration is simple and does not need expensive equipment. It also allows the flexibility to either infiltrate the entire leave with one target gene, or to introduce genes of multiple targets on one leaf. Thus, it can be used for laboratory scale expression of recombinant proteins as well as for comparing different proteins or vectors for yield or expression kinetics. The simplicity of syringe infiltration also suggests its utility in high school and college education for the subject of biotechnology. In contrast, vacuum infiltration is more robust and can be scaledup for commercial manufacture of pharmaceutical proteins. It also offers the advantage of being able to agroinfiltrate plant species that are not amenable for syringe infiltration such as lettuce and Arabidopsis. Overall, the combination of syringe and vacuum agroinfiltration provides researchers and educators a simple, efficient, and robust methodology for transient protein expression. It will greatly facilitate the development of pharmaceutical proteins and promote science education. Video LinkThe video component of this article can be found at

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“…The main targets for subunit vaccine development have been its principal surface antigen hemagglutinin (HA), which plays a major role in functional activity of the virus and is also a main target for neutralizing antibodies of the host, and the M2e viral peptide, the extracellular domain of the viral protein M2, which is highly conserved between various influenza strains and therefore a promising candidate for a universal influenza vaccine. H5N1 HA has been expressed in N. benthamiana in full-length (Kalthoff et al, 2010) and in the form of VLPs (Landry et al, 2010), in Lotus corniculatus (Guo et al, 2012) and most recently, duckweed (Bertran et al, 2015). In addition, recombinant HA from A/Bar-headed Goose/Qinghai/1A/05 (clade 2.2) and A/Anhui/1/2005 (clade 2.3) have been expressed in N. benthamiana (Shoji et al, 2009).…”

Section: Avian Influenza Virus H5n1mentioning

confidence: 99%

Production of vaccines for treatment of infectious diseases by transgenic plants

Ledl

Luthar

2016

AAS

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Since the first pathogen antigen was expressed in transgenic plants with the aim of producing edible vaccine in early 1990s, transgenic plants have become a well-established expression system for production of alternative vaccines against various human and animal infectious diseases. The main focus of plant expression systems in the last five years has been on improving expression of well-studied antigens such as porcine reproductive and respiratory syndrome (PRRSV), bovine viral diarrhea disease virus (BVDV), footh and mouth disease virus (FMDV), hepatitis B surface antigen (HBsAg), rabies G protein, rotavirus, Newcastle disease virus (NDV), Norwalk virus capsid protein (NVCP), avian influenza virus H5N1, Escherichia coli heat-labile enterotoxin subunit B (LT-B), cholera toxin B (CT-B), human immunodeficiency virus (HIV), artherosclerosis, ebola and anthrax. Significant increases in expression have been obtained using improved expression vectors, different plant species and transformation methods.Key words: transgenic plants; vaccine production; recombinant proteins; antibodies; infectious diseases; risk assessment IZVLEČEK ZDRAVLJENJE NALEZLJIVIH BOLEZNI S CEPIVI PRIDOBLJENIMI S TRANSGENIMI RASTLINAMIPridobivanje aktivnih sestavin za cepiva s transgenimi rastlinami se je začelo v devetdesetih letih prejšnjega stoletja. Od takrat se transgene rastline uveljavljajo kot alternativni ekspresijski sistem za sintezo aktivnih komponent za cepiva proti številnim humanim in živalskim nalezljivim boleznim. V zadnjih petih letih je bil glavni poudarek razvoja namenjen optimizaciji rastlinskih ekspresijskih sistemov za dobro proučene antigene, kot so virus prašičjega respiratornega in reproduktivnega sindroma, virus goveje virusne diareje, virus parkljevke, površinski antigen hepatitisa B, G protein virusa stekline, rotavirus, virus atipične kokošje kuge, plaščni protein Norwalk virusa, sev ptičje gripe H5N1, temperaturno nestabilna B podenota enterotoksina Escherischia coli, kolera toksin B, HIV, arterioskleroza, ebola in antraks. Uporaba optimiziranih transformacijskih metod in ekspresijskih vektorjev v kombinaciji s primerno izbrano rastlinsko vrsto je v večini naštetih primerov vodila do opaznega izboljšanja sinteze posameznih učinkovin.

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Preclinical and Clinical Development of Plant-Made Virus-Like Particle Vaccine against Avian H5N1 Influenza

Cited by 261 publications

References 23 publications

Broad and efficient control of major foodborne pathogenic strains of Escherichia coli by mixtures of plant-produced colicins

Broad and efficient control of major foodborne pathogenic strains of Escherichia coli by mixtures of plant-produced colicins

Efficient Agroinfiltration of Plants for High-level Transient Expression of Recombinant Proteins

Production of vaccines for treatment of infectious diseases by transgenic plants

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