Development of plant-produced protein body vaccine candidates for bluetongue virus

Zyl, Albertha R. van; Meyers, Ann E.; Rybicki, Edward P.

doi:10.1186/s12896-017-0370-5

Cited by 10 publications

(6 citation statements)

References 61 publications

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“…Immune responses induced by dual MVA against proteins of RVFV and BTV in mice A number of experimental vaccines for BTV and RVFV have been previously studied in the mouse model based on IFNAR (−/−) mice [22][23][24][25][26][27][28] . Although extrapolation of findings in mice to natural hosts must be done with care due to differences in the biology between mouse and ruminants, experimental infections of IFNAR (−/−) mice with several studied arboviruses, such as BTV and RVFV closely mimics hallmarks of these viruses in their natural host 29 .…”

Section: Expression Of Heterologous Proteins By Mva Vectorsmentioning

confidence: 99%

A protective bivalent vaccine against Rift Valley fever and bluetongue

et al. 2020

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Rift Valley fever (RVF) and bluetongue (BT) are two important ruminant diseases transmitted by arthropods. Both viruses have shown important geographic spread leading to endemicity of BT virus (BTV) in Africa and Europe. In this work, we report a dual vaccine that simultaneously induces protective immune responses against BTV and RVFV based on modified vaccinia Ankara virus (MVA) expressing BTV proteins VP2, NS1, or a truncated form of NS1 (NS1-Nt), and RVFV Gn and Gc glycoproteins. IFNAR (−/−) mice immunized with two doses of MVA-GnGc-VP2 developed a significant neutralizing antibody response against BTV-4 and RVFV. Furthermore, the homologous prime-boost immunization with MVA-GnGc-NS1 or MVA-GnGc-NS1-Nt triggered neutralizing antibodies against RVFV and NS1-specific cytotoxic CD8+ T cells in mice. Moreover, all mice immunized with MVA-GnGc-NS1 or MVA-GnGc-NS1-Nt remained healthy after lethal challenge with RVFV or BTV-4. The homologous prime-boost vaccination with MVA-GnGc-NS1, which was the best immunization strategy observed in mice, was assayed in sheep. Clinical signs and viremia were absent or highly reduced in vaccinated sheep after challenge with BTV-4 or RVFV. These results indicate that MVA-GnGc-NS1 vaccination elicits immune protection against RVFV and BTV in sheep.

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Section: Expression Of Heterologous Proteins By Mva Vectorsmentioning

confidence: 99%

A protective bivalent vaccine against Rift Valley fever and bluetongue

et al. 2020

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“…Even though plant-based production systems are very flexible with respect to upstream production, the downstream processing procedure often includes rate-limiting bottlenecks. For example, in most previous reports, the isolation of PBs from leaf material involved a density gradient ultracentrifugation step (Hofbauer et al, 2016;Joseph et al, 2012;van Zyl, Meyers, & Rybicki, 2017). In the present study, the PBs were recovered by a newly established enrichment process based on several low-speed centrifugations and TFF steps, which can be easily adapted to kg amounts of leaf material without the need to invest in expensive large equipment for continuous ultracentrifugation.…”

Section: Discussionmentioning

confidence: 85%

Plant‐derived protein bodies as delivery vehicles for recombinant proteins into mammalian cells

Schwestka

Tschofen

Vogt

et al. 2020

Biotech & Bioengineering

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The encapsulation of biopharmaceuticals into micro‐ or nanoparticles is a strategy frequently used to prevent degradation or to achieve the slow release of therapeutics and vaccines. Protein bodies (PBs), which occur naturally as storage organelles in seeds, can be used as such carrier vehicles. The fusion of the N‐terminal sequence of the maize storage protein, γ‐zein, to other proteins is sufficient to induce the formation of PBs, which can be used to bioencapsulate recombinant proteins directly in the plant production host. In addition, the immunostimulatory effects of zein have been reported, which are advantageous for vaccine delivery. However, little is known about the interaction between zein PBs and mammalian cells. To better understand this interaction, fluorescent PBs, resulting from the fusion of the N‐terminal portion of zein to a green fluorescent protein, was produced in Nicotiana benthamiana leaves, recovered by a filtration‐based downstream procedure, and used to investigate their internalization efficiency into mammalian cells. We show that fluorescent PBs were efficiently internalized into intestinal epithelial cells and antigen‐presenting cells (APCs) at a higher rate than polystyrene beads of comparable size. Furthermore, we observed that PBs stimulated cytokine secretion by epithelial cells, a characteristic that may confer vaccine adjuvant activities through the recruitment of APCs. Taken together, these results support the use of zein fusion proteins in developing novel approaches for drug delivery based on controlled protein packaging into plant PBs.

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“…The large-scale production of protein bodies requires an effective purification method. Currently, this is usually achieved by gradient ultracentrifugation, which is a barrier to commercial development [ 65 , 86 ]. We recently established an alternative procedure based on serial filtration, which is much more scalable.…”

Section: Plant-derived Microparticles: Storage Organelles For Bioencapsulationmentioning

confidence: 99%

Microparticles and Nanoparticles from Plants—The Benefits of Bioencapsulation

Schwestka

Stöger

2021

Vaccines

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The efficacy of drugs and vaccines depends on their stability and ability to interact with their targets in vivo. Many drugs benefit from encapsulation, which protects them from harsh conditions and allows targeted delivery and controlled release. Although many encapsulation methods are inexpensive, such as the formulation of tablets for oral delivery, others require complex procedures that add significantly to production costs and require low-temperature transport and storage, making them inaccessible in developing countries. In this review we consider the benefits of encapsulation technologies based on plants. Plant-derived biopolymers such as starch and the maize storage protein zein are already used as protective coatings, but plant cells used as production host provide natural in vivo bioencapsulation that survives passage through the stomach and releases drugs in the intestine, due to the presence of microbes that can digest the cell wall. Proteins can also be encapsulated in subcellular compartments such as protein bodies, which ensure stability and activity while often conferring additional immunomodulatory effects. Finally, we consider the incorporation of drugs and vaccines into plant-derived nanoparticles assembled from the components of viruses. These are extremely versatile, allowing the display of epitopes and targeting peptides as well as carrying cargoes of drugs and imaging molecules.

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Development of plant-produced protein body vaccine candidates for bluetongue virus

Cited by 10 publications

References 61 publications

A protective bivalent vaccine against Rift Valley fever and bluetongue

A protective bivalent vaccine against Rift Valley fever and bluetongue

Plant‐derived protein bodies as delivery vehicles for recombinant proteins into mammalian cells

Microparticles and Nanoparticles from Plants—The Benefits of Bioencapsulation

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