Optimization of microcarrier cell culture process for the inactivated enterovirus type 71 vaccine development

作者: S WU , C LIU , W LIAN

DOI: 10.1016/J.VACCINE.2004.05.037

关键词:

摘要: Enterovirus 71 (EV71) is an enterovirus that could lead to severe neurological disorders and fatalities. The inactivated vaccine appropriate EV71 format for meeting current needs. Large-scale preparation of the EV71vaccine depends on a scalable cell culture system industrial mass production. In this paper, Vero cells were found produce higher titers than did MRC-5 WI-38 cells. High-density microcarrier cultures established using 5g/L Cytodex 1 microcarriers promote release EV71s from infected For large-scale production antigen, extracellular virus produced in 2L bioreactor be 10 times lower spinner flask but improved by 30-folds glucose/glutamine feedings during infection. A serum-free was also bioreactor, yielding high-titer 5.8 x 10(7) TCID50/mL immunogenicity virions elicited slightly level neutralizing antibody response immunized mice. These results constitute valuable information development process producing vaccine.

参考文章(28)
Montagnon Bj, Polio and rabies vaccines produced in continuous cell lines: a reality for Vero cell line. Developments in biological standardization. ,vol. 70, pp. 27- 47 ,(1989)
S. A. Locarnini, I. D. Gust, A. P. Yung, C. J. Birch, F. A. Lewis, M. L. Kennett, Enterovirus type 71 infection in Melbourne. Bulletin of The World Health Organization. ,vol. 51, pp. 609- 615 ,(1974)
Sunita Singh, Vincent T.K. Chow, K.P. Chan, A.E. Ling, C.L. Poh, RT-PCR, nucleotide, amino acid and phylogenetic analyses of enterovirus type 71 strains from Asia. Journal of Virological Methods. ,vol. 88, pp. 193- 204 ,(2000) , 10.1016/S0166-0934(00)00185-3
J. M. Berry, N. Barnab�, K. M. Coombs, M. Butler, Production of reovirus type‐1 and type‐3 from Vero cells grown on solid and macroporous microcarriers Biotechnology and Bioengineering. ,vol. 62, pp. 12- 19 ,(1999) , 10.1002/(SICI)1097-0290(19990105)62:1<12::AID-BIT2>3.0.CO;2-G
Chun-Keung Yu, Chi-Chung Chen, Chi-Long Chen, Jen-Ren Wang, Ching-Chuan Liu, Jing-Jou Yan, Ih-Jen Su, Neutralizing antibody provided protection against enterovirus type 71 lethal challenge in neonatal mice. Journal of Biomedical Science. ,vol. 7, pp. 523- 528 ,(2000) , 10.1007/BF02253368
I. Hashimoto, A. Hagiwara, H. Kodama, Neurovirulence in cynomolgus monkeys of enterovirus 71 isolated from a patient with hand, foot and mouth disease. Archives of Virology. ,vol. 56, pp. 257- 261 ,(1978) , 10.1007/BF01317855
Akio Hagiwara, Isamu Tagaya, Tetsuo Yoneyama, Epidemic of Hand, Foot and Mouth Disease Associated with Enterovirus 71 Infection Intervirology. ,vol. 9, pp. 60- 63 ,(1978) , 10.1159/000148922
Ya-Ching Lin, Cheng-Nan Wu, Shin-Ru Shih, Mei-Shang Ho, Characterization of a Vero cell-adapted virulent strain of enterovirus 71 suitable for use as a vaccine candidate. Vaccine. ,vol. 20, pp. 2485- 2493 ,(2002) , 10.1016/S0264-410X(02)00182-2
M. Butler, A. Burgener, M. Patrick, M. Berry, D. Moffatt, N. Huzel, N. Barnabe, K. Coombs, Application of a serum-free medium for the growth of Vero cells and the production of reovirus Biotechnology Progress. ,vol. 16, pp. 854- 858 ,(2000) , 10.1021/BP000110+
J. Blomberg, E. Lycke, K. Ahlfors, T. Johnsson, S. Wolontis, G. Von Zeipel, NEW ENTEROVIRUS TYPE ASSOCIATED WITH EPIDEMIC OF ASEPTIC MENINGITIS AND/OR HAND, FOOT, AND MOUTH DISEASE The Lancet. ,vol. 304, pp. 112- ,(1974) , 10.1016/S0140-6736(74)91684-5