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Fast Single-Use VLP Vaccine Productions Based on Insect Cells and the Baculovirus Expression Vector System: Influenza as Case Study

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Absorption spectrum


Anion exchange chromatography


Cell line from Muscovy duck embryos designed by specialists at Probiogen

A. thaliana :

Arabidopsis thaliana




Baculovirus expression vector system


Baby hamster kidney cell line


Custom biogenic system


Cell concentration at infection: NB CCI is also referred to as time of infection (TOI)


Cluster of differentiation 4 (glycoprotein exposed on the surface of immune cells)


Chicken embryonic fibroblasts


Dendritic cells presenting antigens, used to produce therapeutic cancer vaccines such as Provenge


Dimethyl sulfoxide


Deoxyribonucleic acid


Dissolved oxygen


Dutch-based life and material sciences company


Downstream processing


Cell line derived from chicken embryonic stem cells

E. coli :

Escherichia coli


Enzyme-linked immunospot


Food and Drug Administration


Fluorinated ethylene propylene


Geometric mean titer






High cell density


Cell line derived from human embryonic kidney cells


4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid


Hemagglutinin inhibition


Cell line (also called BTI-TN-5B1-4) originating from the ovarian cells of the cabbage looper, Trichoplusia ni


Human papilloma virus


Insect cell


Immunoglobuline G


High-throughput screening


Ion exchange chromatography


Madin–Darby canine kidney cell line, cells derived from kidney of a cocker spaniel


2-(N-morpholino) ethanolsulfonic acid


Major histocompatibility complex


Multiplicity of infection


Fetal lung cell line


Molecular weight cut-off


Matrix M1


Matrix M2



N. benthanmiana :

Nicotiana benthamiana

N. tabacum :

Nicotiana tabacum


Statistical significance


Phosphate buffered saline


Patented cell line from HepaLife Technologies, cells derived from an immortalized chicken embryo cell


Polymerase chain reaction


Human retinal cell line (owned by Crucell Holland B.V.), that guarantees high product yields (8 g L−1 in fed batch productions of antibodies and 27 g L−1 in antibody production processes based on DSM’s XD technology)

P. pastoris :

Pichia pastoris


Point of harvest, also called time of harvest (TOH)


Plaque-forming units


Post infection


Rocking motion


Ribonucleic acid


Revolutions per minute


Sodium dodecyl sulfate polyacrylamide


Size-exclusion chromatography


Single radial immune diffusion



Sf :

Spodoptera frugiperda

S2 cells:

Schneider 2 cells, representing one of the most commonly used Drosophila melanogaster cell lines

TCID50 :

50 % tissue culture infection dose


Transmembrane pressure


Time of harvest


Time of infection


Upstream processing


Cell line derived from the kidney of an American green monkey


Virus like particle


Recombinant seed virus rBVH1N1-PR834


Master seed virus


Working seed virus used to generate the WVB


Volume per volume per minute


Working cell bank


Working virus bank

XD technology:

Highly intensified cell culture process with titers up to 15 times higher than current standard production processes for biotherapeutics


Zurich University of Applied Sciences


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We would like to thank Nathalie Riesen and Christoph Ries (ZHAW, Wädenswil, CH) for their assistance regarding design and analysis of the VLP production experiments as well as Nicole Imseng (ZHAW, Wädenswil, CH) for her practical support and proofreading. Armando Zuniga (Redbiotec AG, Schlieren, CH), Brock Kingstad-Bakke, Joseph Brewoo, and Jorge Osorio (all University of Wisconsin–Madison, USA) are acknowledged for the execution and interpretation of the mouse preclinical studies. Julia Friesen, Matthias Meier, and Dorothea Karrer (all Redbiotec AG, Schlieren, CH) receive our gratitude for their excellent laboratory support. We also thank Christian Schaub for taking overall responsibility and providing support for the project at Redbiotec AG. This work was supported by the Commission for Technology and Innovation based in Switzerland.

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Eibl, R., Steiger, N., Wellnitz, S., Vicente, T., John, C., Eibl, D. (2013). Fast Single-Use VLP Vaccine Productions Based on Insect Cells and the Baculovirus Expression Vector System: Influenza as Case Study. In: Eibl, D., Eibl, R. (eds) Disposable Bioreactors II. Advances in Biochemical Engineering/Biotechnology, vol 138. Springer, Berlin, Heidelberg.

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