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
[21]   Monitoring influenza virus content in vaccine production:: Precise assays for the quantitation of hemagglutination and neuraminidase activity [J].
Kalbfuss, Bernd ;
Knoechlein, Anne ;
Kroeber, Tina ;
Reichl, Udo .
BIOLOGICALS, 2008, 36 (03) :145-161
[22]  
Kamen AA, 1996, BIOTECHNOL BIOENG, V50, P36
[23]   HPLC-based quantification of haemagglutinin in the production of egg- and MDCK cell-derived influenza virus seasonal and pandemic vaccines [J].
Kapteyn, J. C. ;
Porre, A. M. ;
de Rond, E. J. R. ;
Hessels, W. B. ;
Tijms, M. A. ;
Kessen, H. ;
Slotboom, A. M. E. ;
Oerlemans, M. A. ;
Smit, D. ;
van der Linden, J. ;
Schoen, P. ;
Thus, J. L. G. .
VACCINE, 2009, 27 (09) :1468-1477
[24]   Haemagglutinin quantification and identification of influenza A&B strains propagated in PER.C6® cells:: A novel RP-HPLC method [J].
Kapteyn, JC ;
Saidi, MD ;
Dijkstra, R ;
Kars, C ;
Tjon, JCMSK ;
Weverling, GJ ;
de Vocht, ML ;
Kompier, R ;
van Montfort, BA ;
Guichoux, JY ;
Goudsmit, J ;
Lagerwerf, FM .
VACCINE, 2006, 24 (16) :3137-3144
[25]  
Karber G, 1931, EXP PATHOL PHARM, V162, P480
[26]   Development of a mammalian cell (Vero) derived candidate influenza virus vaccine [J].
Kistner, O ;
Barrett, PN ;
Mundt, W ;
Reiter, M ;
Schober-Bendixen, S ;
Dorner, F .
VACCINE, 1998, 16 (9-10) :960-968
[27]   ACTIVATION OF INFLUENZA-A VIRUSES BY TRYPSIN TREATMENT [J].
KLENK, HD ;
ROTT, R ;
ORLICH, M ;
BLODORN, J .
VIROLOGY, 1975, 68 (02) :426-439
[28]   REAL-TIME BIOMASS-CONCENTRATION MONITORING IN ANIMAL-CELL CULTURES [J].
KONSTANTINOV, K ;
CHUPPA, S ;
SAJAN, E ;
TSAI, Y ;
YOON, SJ ;
GOLINI, F .
TRENDS IN BIOTECHNOLOGY, 1994, 12 (08) :324-333
[29]  
Kurokawa M, 1999, INT J MOL MED, V3, P527
[30]   MONITORING OF MAMMALIAN-CELL GROWTH AND VIRUS PRODUCTION PROCESS USING ONLINE OXYGEN-UPTAKE RATE MEASUREMENT [J].
KUSSOW, CM ;
ZHOU, WC ;
GRYTE, DM ;
HU, WS .
ENZYME AND MICROBIAL TECHNOLOGY, 1995, 17 (09) :779-783