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
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