Scalable production of influenza virus in HEK-293 cells for efficient vaccine manufacturing

被引:101
作者
Le Ru, Audrey [1 ,2 ]
Jacob, Danielle [1 ]
Transfiguracion, Julia [1 ]
Ansorge, Sven [1 ,2 ]
Henry, Olivier [2 ]
Kamen, Amine A. [1 ,2 ]
机构
[1] Natl Res Council Canada, Montreal, PQ H4P 2R2, Canada
[2] Ecole Polytech, Dept Chem Engn, Montreal, PQ H3T 1J4, Canada
关键词
Influenza virus; HEK-293; Suspension culture; Serum-free medium; Bioreactor; Vaccine production; RECOMBINANT PROTEIN; EXPRESSION SYSTEM; VECTOR PRODUCTION; MDCK CELLS; HIGH-YIELD; A VIRUSES; CULTURE; SERUM; HEMAGGLUTININ; INFECTION;
D O I
10.1016/j.vaccine.2010.03.029
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cell culture processes offer an attractive alternative to conventional chicken egg-based influenza vaccine production methods. However, most protocols still rely on the use of adherent cells, which makes process scale-up a challenging issue. In this study, it is demonstrated that the HEK-293 human cell line is able to efficiently replicate influenza virus. Production in serum-free suspension of HEK-293 cultures resulted in high titers of infectious influenza viruses for different subtypes and variants including A/H1, A/H3 and B strains. After virus adaptation and optimization of infection conditions, production in 3-L bioreactor resulted in titers of up to 10(9) IVP/mL demonstrating the scale-up potential of the process. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:3661 / 3671
页数:11
相关论文
共 55 条
[1]   RAPID VIRUS SUBUNIT VISUALIZATION BY DIRECT SEDIMENTATION OF SAMPLES ON ELECTRON-MICROSCOPE GRIDS [J].
ALAIN, R ;
NADON, F ;
SEGUIN, C ;
PAYMENT, P ;
TRUDEL, M .
JOURNAL OF VIROLOGICAL METHODS, 1987, 16 (03) :209-216
[2]   Development of a scalable process for high-yield lentiviral vector production by transient transfection of HEK293 suspension cultures [J].
Ansorge, Sven ;
Lanthier, Stephane ;
Transfiguracion, Julia ;
Durocher, Yves ;
Henry, Olivier ;
Kamen, Amine .
JOURNAL OF GENE MEDICINE, 2009, 11 (10) :868-876
[3]   Host defense, viruses and apoptosis [J].
Barber, GN .
CELL DEATH AND DIFFERENTIATION, 2001, 8 (02) :113-126
[4]   Influenza vaccines: recent advances in production technologies [J].
Bardiya, N ;
Bae, JH .
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, 2005, 67 (03) :299-305
[5]  
Belsey M., 2005, J Commercial Biotechnol, V12, P150
[6]   Influenza vaccines [J].
Belsey, MJ ;
de Lima, B ;
Pavlou, AK ;
Savopoulos, JW .
NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (03) :183-184
[7]   Study of adenovirus production in serum-free 293SF suspension culture by GFP-expression monitoring [J].
Cote, J ;
Bourget, L ;
Garnier, A ;
Kamen, A .
BIOTECHNOLOGY PROGRESS, 1997, 13 (06) :709-714
[8]  
Côté J, 1998, BIOTECHNOL BIOENG, V59, P567, DOI 10.1002/(SICI)1097-0290(19980905)59:5<567::AID-BIT6>3.0.CO
[9]  
2-8
[10]   High-level and high-throughput recombinant protein production by transient transfection of suspension-growing human 293-EBNA1 cells [J].
Durocher, Y ;
Perret, S ;
Kamen, A .
NUCLEIC ACIDS RESEARCH, 2002, 30 (02) :E9