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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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Abbreviations

ABS:

Absorption spectrum

AEX:

Anion exchange chromatography

AGE1.CR:

Cell line from Muscovy duck embryos designed by specialists at Probiogen

A. thaliana :

Arabidopsis thaliana

BV:

Baculovirus

BEVS:

Baculovirus expression vector system

BHK-21:

Baby hamster kidney cell line

CBS:

Custom biogenic system

CCI:

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

CD4:

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

CEFs:

Chicken embryonic fibroblasts

DCs:

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

DMSO:

Dimethyl sulfoxide

DNA:

Deoxyribonucleic acid

DO:

Dissolved oxygen

DSM:

Dutch-based life and material sciences company

DSP:

Downstream processing

EB14:

Cell line derived from chicken embryonic stem cells

E. coli :

Escherichia coli

ELISPOT:

Enzyme-linked immunospot

FDA:

Food and Drug Administration

FEP:

Fluorinated ethylene propylene

GMT:

Geometric mean titer

GSK:

GlaxoSmithKline

HA:

Hemagglutinin

HCD:

High cell density

HEK293:

Cell line derived from human embryonic kidney cells

HEPES:

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

HI:

Hemagglutinin inhibition

Hi-5:

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

HPV:

Human papilloma virus

IC:

Insect cell

IgG:

Immunoglobuline G

HTS:

High-throughput screening

IEX:

Ion exchange chromatography

MDCK:

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

MES:

2-(N-morpholino) ethanolsulfonic acid

MHC:

Major histocompatibility complex

MOI:

Multiplicity of infection

MRC-5:

Fetal lung cell line

MWCO:

Molecular weight cut-off

M1:

Matrix M1

M2:

Matrix M2

NA:

Neuraminidase

N. benthanmiana :

Nicotiana benthamiana

N. tabacum :

Nicotiana tabacum

P:

Statistical significance

PBS:

Phosphate buffered saline

PBS-1:

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

PCR:

Polymerase chain reaction

PERC.-6:

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

POH:

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

pfu:

Plaque-forming units

p.i.:

Post infection

RM:

Rocking motion

RNA:

Ribonucleic acid

rpm:

Revolutions per minute

SDS-Page:

Sodium dodecyl sulfate polyacrylamide

SEC:

Size-exclusion chromatography

SRD:

Single radial immune diffusion

SU:

Single-use

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

TMP:

Transmembrane pressure

TOH:

Time of harvest

TOI:

Time of infection

USP:

Upstream processing

Vero:

Cell line derived from the kidney of an American green monkey

VLP:

Virus like particle

V0:

Recombinant seed virus rBVH1N1-PR834

V1:

Master seed virus

V2:

Working seed virus used to generate the WVB

vvm:

Volume per volume per minute

WCB:

Working cell bank

WVB:

Working virus bank

XD technology:

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

ZHAW:

Zurich University of Applied Sciences

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Acknowledgments

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. https://doi.org/10.1007/10_2013_186

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