Production of rVSV-ZEBOV in serum-free suspension culture of HEK 293SF cells

Jean François Gélinas, Hiva Azizi, Sascha Kiesslich, Stéphane Lanthier, Jannie Perdersen, Parminder S. Chahal, Sven Ansorge, Gary Kobinger, Rénald Gilbert, Amine A. Kamen

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Ebola virus disease is an urgent international priority. Promising results for several vaccine candidates have been reported in non-human primate studies and clinical trials with the most promising being the rVSV-ZEBOV vaccine. In this study, we sought to produce rVSV-ZEBOV in HEK 293SF cells in suspension and serum-free media. The purpose of this study was to establish a process using the HEK 293SF production platform, optimise the production titre, demonstrate scalability and the efficiency of the generated material to elicit an immune reaction in an animal model. Critical process parameters were evaluated to maximize production yield and process robustness and the following operating conditions: 1–2 × 106 cells/mL grown in HyClone HyCell TransFx-H media infected at an MOI of 0.001 with a temperature shift to 34 °C during the production phase and a harvest of the product after 48 h. Using these conditions, scalability in a 3.5 L controlled bioreactor was shown reaching a titre of 1.19 × 108 TCID50/mL at the peak of production, the equivalent of 4165 doses of vaccine per litre. The produced virus was shown to be thermostable in the culture media and, when concentrated, purified and administered to mice, demonstrated the ability to induce a ZEBOV-specific immune response.

Original languageEnglish (US)
Pages (from-to)6624-6632
Number of pages9
JournalVaccine
Volume37
Issue number44
DOIs
StatePublished - Oct 16 2019
Externally publishedYes

Keywords

  • Ebola
  • HEK 293SF
  • Production
  • Serum-free
  • Suspension
  • Vaccine
  • rVSV-ZEBOV

ASJC Scopus subject areas

  • Molecular Medicine
  • General Immunology and Microbiology
  • General Veterinary
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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