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Interferon Inhibition Enhances the Pilot-Scale Production of Rabies Virus in Human Diploid MRC-5 Cells.

Publication ,  Journal Article
Yang, X; Wan, M; Cai, L; Hou, A; Sun, B; Zhou, Y; Gao, F; Su, W; Jiang, C
Published in: Viruses
December 29, 2021

Inactivated vaccines based on cell culture are very useful in the prevention and control of many diseases. The most popular strategy for the production of inactivated vaccines is based on monkey-derived Vero cells, which results in high productivity of the virus but has a certain carcinogenic risk due to non-human DNA contamination. Since human diploid cells, such as MRC-5 cells, can produce a safer vaccine, efforts to develop a strategy for inactivated vaccine production using these cells have been investigated using MRC-5 cells. However, most viruses do not replicate efficiently in MRC-5 cells. In this study, we found that rabies virus (RABV) infection activated a robust interferon (IFN)-β response in MRC-5 cells but almost none in Vero cells, suggesting that the IFN response could be a key limiting factor for virus production. Treatment of the MRC-5 cells with IFN inhibitors increased RABV titers by 10-fold. Additionally, the RABV titer yield was improved five-fold when using IFN receptor 1 (IFNAR1) antibodies. As such, we established a stable IFNAR1-deficient MRC-5 cell line (MRC-5IFNAR1-), which increased RABV production by 6.5-fold compared to normal MRC-5 cells. Furthermore, in a pilot-scale production in 1500 square centimeter spinner flasks, utilization of the MRC-5IFNAR1- cell line or the addition of IFN inhibitors to MRC cells increased RABV production by 10-fold or four-fold, respectively. Thus, we successfully established a human diploid cell-based pilot scale virus production platform via inhibition of IFN response for rabies vaccines, which could also be used for other inactivated virus vaccine production.

Duke Scholars

Published In

Viruses

DOI

EISSN

1999-4915

Publication Date

December 29, 2021

Volume

14

Issue

1

Location

Switzerland

Related Subject Headings

  • Vero Cells
  • Vaccines, Inactivated
  • Receptor, Interferon alpha-beta
  • Rabies virus
  • Rabies Vaccines
  • Rabies
  • Interferons
  • Humans
  • Gene Expression
  • Diploidy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yang, X., Wan, M., Cai, L., Hou, A., Sun, B., Zhou, Y., … Jiang, C. (2021). Interferon Inhibition Enhances the Pilot-Scale Production of Rabies Virus in Human Diploid MRC-5 Cells. Viruses, 14(1). https://doi.org/10.3390/v14010049
Yang, Xiao, Mingming Wan, Linjun Cai, Ali Hou, Bo Sun, Yan Zhou, Feng Gao, Weiheng Su, and Chunlai Jiang. “Interferon Inhibition Enhances the Pilot-Scale Production of Rabies Virus in Human Diploid MRC-5 Cells.Viruses 14, no. 1 (December 29, 2021). https://doi.org/10.3390/v14010049.
Yang X, Wan M, Cai L, Hou A, Sun B, Zhou Y, et al. Interferon Inhibition Enhances the Pilot-Scale Production of Rabies Virus in Human Diploid MRC-5 Cells. Viruses. 2021 Dec 29;14(1).
Yang, Xiao, et al. “Interferon Inhibition Enhances the Pilot-Scale Production of Rabies Virus in Human Diploid MRC-5 Cells.Viruses, vol. 14, no. 1, Dec. 2021. Pubmed, doi:10.3390/v14010049.
Yang X, Wan M, Cai L, Hou A, Sun B, Zhou Y, Gao F, Su W, Jiang C. Interferon Inhibition Enhances the Pilot-Scale Production of Rabies Virus in Human Diploid MRC-5 Cells. Viruses. 2021 Dec 29;14(1).

Published In

Viruses

DOI

EISSN

1999-4915

Publication Date

December 29, 2021

Volume

14

Issue

1

Location

Switzerland

Related Subject Headings

  • Vero Cells
  • Vaccines, Inactivated
  • Receptor, Interferon alpha-beta
  • Rabies virus
  • Rabies Vaccines
  • Rabies
  • Interferons
  • Humans
  • Gene Expression
  • Diploidy