purification strategies, 178–189
quantification of influenza virus, 231–233
recombinant vaccines, gag-based VLPs, 239–268
additives to increase transient transfection,
248–249
cell culture modes, 249–256
cell lines/plasmids, 248
characterization/quantification of VLPs,
258–259
examples of GAG-based VLPs, 256
HIV-1 GAG VLPs, 241–245
improving production process, 247–256
optimization of TGE, 248
PEI-mediated transient transfection, 245–247
production of HIV-1 GAG VLPs, 245–247
scalable DSP for HIV-1 GAG VLPs, 256–258
serum-free media, 247–248
virus-like particles, 239–241
regulation of vaccines, 5–6, 304–307
adenovirus vectored COVID-19 vaccines,
306–307
adenovirus vectored vaccines, 305
protein sub-unit vaccines, 308–310
whole virus vaccines, 307–308
RNA vaccines, 299–304
mRNA vaccine design, 300–301
mRNA vaccine manufacturing, 301–302
stability/efficacy of mRNA vaccines, 302–304
safety of vaccines, 5–6
SARS-COV-2, 297–310
biology, 295–296
immunology/vaccine rationale, 296–297
seed virus generation, 113
spin filters, 152–153
structure, 19–22
subunit vaccine, 51–52
T-cell recognition, 46
tangential flow filtration, 153–155
total viral particles quantification, 208–217
traditional methods for virus purification, 177–178
traditional production, 6–8
upstream processing, 79–174
adherent vs. suspension cells, 92–95
batch cultures to intensified processes,
143–146
biosafety, 125–127
cell attachment and use of microcarriers,
94–95
cell banking, 90–91
cell lines/ virus production, 87–95
cell retention devices, 149–163
acoustic settler, 162–163
alternating tangential flow, 155–157
disc centrifuge, 157–159
hydrocyclone, 160–161
inclined settler, 159–160
spin filters, 152–153
tangential flow filtration, 153–155
CMC/GMP considerations, 120–125
cell growth and harvesting, 123–124
cellular sources, 122–123
purification and downstream processing,
124–125
virus sources, 123
critical factors for virus production at high cell
density, 146–149
cultivation media/metabolism, 95–102
media and additives, 95–100
monitoring cell metabolism, 100–102
cultivation vessels, 102–110
process variables, 105–109
oxygen supply, 107–109
pH and CO2, 106
shear stress, 106–107
temperature, 106
production vessel, 110
disposables, 163–166
manufacturing options, 125
motivation for process intensification,
139–140
parameters for process comparison/
evaluation, 140–143
preculture/maintenance of cells, 91–92
process development/optimization, 112–119
options, 113–119
selection of host cell lines, 87–90
trouble shooting, 119–120
vaccine candidates, 83–87
virus production/process development,
110–119
seed virus generation, 113
virus production, 110–112
vaccine market, 4–5
vectored vaccines, 269–292
adenovirus-vectored vaccines, 270–281
AdV-based COVID-19 vaccine, 280–281
AdV-based Ebola vaccine, 280
AdV structure and vector design, 276–277
cell line selection, 277
examples of AdV-based vaccines,
279–281
limitations in production of AdV, 277–278
production process of AdV vectors,
277–279
productivity of AdV, 278–279
quantitation methods of AdV vector, 279
Index
317