Vero cells in roller bottles [72]. For cost-effective manufacturing, more scalable
bioprocesses including fixed-bed bioreactors and microcarrier bioreactors have been
developed [71]. However, the use of adherent cells still has scale-up limitations. For
example, in cell expansion steps, the cells are required to detach and re-attach
to surfaces involving enzymatic solutions such as trypsin, which complicate the
process. For process scale-up, adaptation of anchorage-dependent cells to suspen-
sion cultures is valuable, since the transfer of cells to larger bioreactors is
straightforward. In addition, serum is needed in most cell growth. However, the
addition of serum presents critical drawbacks including the risk of hypersensitivity,
serum variability, and contaminations. Therefore, the requirement of biological
safety motivated industries to develop serum-free media.
Some successful results of adaptation have been reported using proprietary media.
Shen et al. adapted the Vero cells to suspension culture and growth in serum-free
media. They successfully use the system to produce rVSV-GFP in batch and perfu-
sion bioreactors [73]. Kiesslich et al. further adapted the Vero cells to grow in a
commercially available medium. In addition, they produced different constructions
of rVSV including rVSV-ZEBOV, rVSV-HIV, and rVSVInd-msp-SF-Gtc [71].
Additionally, Elahi et al. produced VSV-GFP in suspension cell culture and serum-
free medium using, HEK293SF-3F6 derived from HEK293A cells and SF-BMAdR
cells (a variant of A549) [45].
TABLE 11.3
Clinical trials involving VSV vector a
Vector
Target
Disease
Number of trials
in phase 1/2 and
2, 3, & 4
NCT number
VSV
Infectious
diseases
Ebolaviruses
4 (phase 1)
NCT02280408;
NCT04906629;
NCT02933931;
NCT02314923
HIV
2 (phase 1)
NCT01438606;
NCT01578889
COVID-19
1 (phase 2/3)
NCT04990466
Therapeutic
cancer vaccines
Melanoma
1 (phase 1)
NCT03865212
Solid tumor
1 (phase 1)
NCT02923466
1 (phase 1/2)
NCT03647163
Head/neck/lung
1 (phase 1/2)
NCT03647163
Endometrial
cancer
1 (phase 1)
NCT03456908
Note
a Data from https://clinicaltrials.gov.
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Bioprocessing of Viral Vaccines