Highly efficient purification of recombinant vsv-∆g-spike vaccine against sars-cov-2 by flow-through chromatography

Elad Lerer, Ziv Oren, Yaron Kafri, Yaakov Adar, Einat Toister, Lilach Cherry, Edith Lupu, Arik Monash, Rona Levy, Eyal Dor, Eyal Epstein, Lilach Levin, Meni Girshengorn, Niva Natan, Ran Zichel, Arik Makovitzki

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


This study reports a highly efficient, rapid one-step purification process for the production of the recombinant vesicular stomatitis virus-based vaccine, rVSV-∆G-spike (rVSV-S), recently de-veloped by the Israel Institute for Biological Research (IIBR) for the prevention of COVID-19. Several purification strategies are evaluated using a variety of chromatography methods, including membrane adsorbers and packed-bed ion-exchange chromatography. Cell harvest is initially treated with endonuclease, clarified, and further concentrated by ultrafiltration before chromatography purification. The use of anion-exchange chromatography in all forms results in strong binding of the virus to the media, necessitating a high salt concentration for elution. The large virus and spike protein binds very strongly to the high surface area of the membrane adsorbents, resulting in poor virus recovery (<15%), while the use of packed-bed chromatography, where the surface area is smaller, achieves better recovery (up to 33%). Finally, a highly efficient chromatography purification process with Capto™ Core 700 resin, which does not require binding and the elution of the virus, is described. rVSV-S cannot enter the inner pores of the resin and is collected in the flow-through eluent. Purification of the rVSV-S virus with Capto™ Core 700 resulted in viral infectivity above 85% for this step, with the efficient removal of host cell proteins, consistent with regulatory requirements. Similar results were obtained without an initial ultrafiltration step.

Original languageEnglish
Article number22
Issue number4
StatePublished - 12 Oct 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Chromatography
  • Downstream process
  • Membrane adsorbers
  • SARS-CoV-2
  • rVSV


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