Enhancing enterovirus A71 vaccine production yield by microcarrier profusion bioreactor culture

Chia Chyi Liu, Suh Chin Wu, Shang-Rung Wu, Hsiao Yu Lin, Meng Shin Guo, Alan Yung-Chih Hu, Yen Hung Chow, Jen Ron Chiang, Dar-Bin Shieh, Pele Chong

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Hand, foot and mouth diseases (HFMD) are mainly caused by Enterovirus A71 (EV-A71) infections. Clinical trials in Asia conducted with formalin-inactivated EV-A71 vaccine candidates produced from serum-free Vero cell culture using either roller bottle or cell factory technology, are found to be safe and highly efficacious. To increase vaccine yields and reduce the production costs, the bioprocess improvement for EV-A71 vaccine manufacturing is currently being investigated. The parameters that could affect and enhance the production yields of EV-A71 virus growth in the microcarrier bioreactor were investigated. The medium replacement culture strategy included a multi-harvested semi-batch process and perfusion technology and was found to increase the production yields more than 7–14 folds. Based on the western blot and cryo-EM analyses of the EV-A71 virus particles produced from either the multi-harvested semi-batch (MHSBC) or perfusion cultures were found to be similar to those virus particles obtained from the single batch culture. Mouse immunogenicity studies indicate that the EV-A71 vaccine candidates produced from the perfusion culture have similar potency to those obtained from single batch bioprocess. The physical structures of the EV-A71 particles revealed by the cryo-EM analysis were found to be spherical capsid particles. These results provide feasible technical bioprocesses for increasing virus yields and the scale up of EV-A71 vaccine manufacturing using the bioreactor cell culture methods.

Original languageEnglish
Pages (from-to)3134-3139
Number of pages6
JournalVaccine
Volume36
Issue number22
DOIs
Publication statusPublished - 2018 May 24

Fingerprint

Enterovirus
Bioreactors
bioreactors
Vaccines
vaccines
Perfusion
Virion
virion
Cell Culture Techniques
Hand, Foot and Mouth Disease
manufacturing
Enterovirus Infections
cell culture
Viruses
Technology
hand, foot and mouth disease
Batch Cell Culture Techniques
Vero Cells
Capsid
viruses

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Liu, C. C., Wu, S. C., Wu, S-R., Lin, H. Y., Guo, M. S., Yung-Chih Hu, A., ... Chong, P. (2018). Enhancing enterovirus A71 vaccine production yield by microcarrier profusion bioreactor culture. Vaccine, 36(22), 3134-3139. https://doi.org/10.1016/j.vaccine.2017.02.042
Liu, Chia Chyi ; Wu, Suh Chin ; Wu, Shang-Rung ; Lin, Hsiao Yu ; Guo, Meng Shin ; Yung-Chih Hu, Alan ; Chow, Yen Hung ; Chiang, Jen Ron ; Shieh, Dar-Bin ; Chong, Pele. / Enhancing enterovirus A71 vaccine production yield by microcarrier profusion bioreactor culture. In: Vaccine. 2018 ; Vol. 36, No. 22. pp. 3134-3139.
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Liu, CC, Wu, SC, Wu, S-R, Lin, HY, Guo, MS, Yung-Chih Hu, A, Chow, YH, Chiang, JR, Shieh, D-B & Chong, P 2018, 'Enhancing enterovirus A71 vaccine production yield by microcarrier profusion bioreactor culture', Vaccine, vol. 36, no. 22, pp. 3134-3139. https://doi.org/10.1016/j.vaccine.2017.02.042

Enhancing enterovirus A71 vaccine production yield by microcarrier profusion bioreactor culture. / Liu, Chia Chyi; Wu, Suh Chin; Wu, Shang-Rung; Lin, Hsiao Yu; Guo, Meng Shin; Yung-Chih Hu, Alan; Chow, Yen Hung; Chiang, Jen Ron; Shieh, Dar-Bin; Chong, Pele.

In: Vaccine, Vol. 36, No. 22, 24.05.2018, p. 3134-3139.

Research output: Contribution to journalArticle

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