Enhanced production yields of rVSV-SARS-CoV-2 vaccine using Fibra-Cel ® macrocarriers

The COVID-19 pandemic has led to high global demand for vaccines to safeguard public health. To that end, our institute has developed a recombinant viral vector vaccine utilizing a modified vesicular stomatitis virus (VSV) construct, wherein the G protein of VSV is replaced with the spike protein of...

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Published in:	Frontiers in bioengineering and biotechnology Vol. 12; p. 1333548
Main Authors:	Cohen, Noam, Simon, Irit, Hazan, Ophir, Tal, Arnon, Tzadok, Hanan, Levin, Lilach, Girshengorn, Meni, Mimran, Lilach Cherry, Natan, Niva, Baruhi, Tzadok, David, Alon Ben, Rosen, Osnat, Shmaya, Shlomo, Borni, Sarah, Cohen, Noa, Lupu, Edith, Kedmi, Adi, Zilberman, Orian, Jayson, Avital, Monash, Arik, Dor, Eyal, Diamant, Eran, Goldvaser, Michael, Cohen-Gihon, Inbar, Israeli, Ofir, Lazar, Shirley, Shifman, Ohad, Beth-Din, Adi, Zvi, Anat, Oren, Ziv, Makovitzki, Arik, Lerer, Elad, Mimran, Avishai, Toister, Einat, Zichel, Ran, Adar, Yaakov, Epstein, Eyal
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 21-02-2024
Subjects:	Bioengineering and Biotechnology bioprocess fixed-bed bioreactor genetic stability production virus vaccine VSV VSV fixed-bed bioreactor bioprocess genetic stability production virus vaccine
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Summary:	The COVID-19 pandemic has led to high global demand for vaccines to safeguard public health. To that end, our institute has developed a recombinant viral vector vaccine utilizing a modified vesicular stomatitis virus (VSV) construct, wherein the G protein of VSV is replaced with the spike protein of SARS-CoV-2 (rVSV-ΔG-spike). Previous studies have demonstrated the production of a VSV-based vaccine in Vero cells adsorbed on Cytodex 1 microcarriers or in suspension. However, the titers were limited by both the carrier surface area and shear forces. Here, we describe the development of a bioprocess for rVSV-ΔG-spike production in serum-free Vero cells using porous Fibra-Cel macrocarriers in fixed-bed BioBLU 320 5p bioreactors, leading to high-end titers. We identified core factors that significantly improved virus production, such as the kinetics of virus production, the use of for oxygen supply, and medium replenishment. Implementing these parameters, among others, in a series of GMP production processes improved the titer yields by at least two orders of magnitude (2e9 PFU/mL) over previously reported values. The developed process was highly effective, repeatable, and robust, creating potent and genetically stable vaccine viruses and introducing new opportunities for application in other viral vaccine platforms.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Karla Mayolo-Deloisa, Institute for Obesity Research, Mexico These authors have contributed equally to this work Reviewed by: Tanya Amanda Camacho-Villegas, CONACYT Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Mexico Edited by: Cecília Calado, Lisbon Higher Institute of Engineering (ISEL), Portugal Deceased
ISSN:	2296-4185 2296-4185
DOI:	10.3389/fbioe.2024.1333548