Viral Vaccine Production in Cell Culture

Auniņš, John G.

doi:10.1002/0471250570.spi105

Cited by 22 publications

(28 citation statements)

References 481 publications

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“…Finally, virus concentration decrease as production stop and the newly synthesized virus decays under culture conditions. 19 Experimental conditions 37 C temperature in combination with 24 h time of infection showed the worst viral production results ( Figure 3D) and they are not appropriated for large-scale bioprocess.…”

Section: Discussionmentioning

confidence: 97%

“…23 This explains the virus disappearance, immediately after virus inoculation, in most of assessed temperature and time of infection, when virus is attaching and penetrating cells. 19 Probably, this process is not observed in some experimental condition because of chosen harvest time spacing. Subsequently of this infection phase, an "eclipse" phase was detected, in which rabies virus reach a minimum in supernatant, when early events of intracellular replication take place.…”

Section: Discussionmentioning

confidence: 99%

“…The growth of a fastidious host cell agent (virus) should be optimize and performed in a very strict processing and regulatory environment at affordable cost. 19 Several process parameters define the success of these bioprocesses, among them are included: culture medium composition and feed strategy, temperature, pH, multiplicity of infection, time of infection, harvest time. The big challenge comprising virus production is to find a set of values for parameters mentioned above in order to maximize the difference between viral production and degradation.…”

Section: Discussionmentioning

confidence: 99%

“…The big challenge comprising virus production is to find a set of values for parameters mentioned above in order to maximize the difference between viral production and degradation. [19][20][21] Whereas the processes of viral infection are influenced by many variables, the optimal combination of parameters varies greatly in different virus-host cell systems, and there are few phenomenological mathematical models that describe the processes of viral production. For this reason, it is useful to develop small scale experimental strategies that can deliver at relatively low cost optimization of these processes.…”

Section: Discussionmentioning

confidence: 99%

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Use of uniform designs in combination with neural networks for viral infection process development

Buenno¹,

Rocha²,

Leme

et al. 2015

Biotechnology Progress

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This work aimed to compare the predictive capacity of empirical models, based on the uniform design utilization combined to artificial neural networks with respect to classical factorial designs in bioprocess, using as example the rabies virus replication in BHK-21 cells. The viral infection process parameters under study were temperature (34°C, 37°C), multiplicity of infection (0.04, 0.07, 0.1), times of infection, and harvest (24, 48, 72 hours) and the monitored output parameter was viral production. A multilevel factorial experimental design was performed for the study of this system. Fractions of this experimental approach (18, 24, 30, 36 and 42 runs), defined according uniform designs, were used as alternative for modelling through artificial neural network and thereafter an output variable optimization was carried out by means of genetic algorithm methodology. Model prediction capacities for all uniform design approaches under study were better than that found for classical factorial design approach. It was demonstrated that uniform design in combination with artificial neural network could be an efficient experimental approach for modelling complex bioprocess like viral production. For the present study case, 67% of experimental resources were saved when compared to a classical factorial design approach. In the near future, this strategy could replace the established factorial designs used in the bioprocess development activities performed within biopharmaceutical organizations because of the improvements gained in the economics of experimentation that do not sacrifice the quality of decisions.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Use of uniform designs in combination with neural networks for viral infection process development

Buenno¹,

Rocha²,

Leme

et al. 2015

Biotechnology Progress

View full text Add to dashboard Cite

show abstract

“…Besides, mammalian cell culture is used widely in lab scale for performing researches about several diseases as well as new drug screening and safety testing (Griffiths and Wurm 2003). Specially, BHK-21 has also been employed extensively for veterinarian viral vaccines (foot-and-mouth disease virus and rabies virus) since 1960s (Auninš 2010).…”

Section: Introductionmentioning

confidence: 99%

Approach toward an efficient inoculum preparation stage for suspension BHK-21 cell culture

et al. 2014

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Mammalian cells are the most frequently used hosts for biopharmaceutical proteins manufacturing. Inoculum quality is a key element for establishing an efficient bioconversion process. The main objective in inoculation expansion process is to generate large volume of viable cells in the shortest time. The aim of this paper was to optimize the inoculum preparation stage of baby hamster kidney (BHK)-21 cells for suspension cultures in benchtop bioreactors, by means of a combination of static and agitated culture systems. Critical parameters for static (liquid column height: 5, 10, 15 mm) and agitated (working volume: 35, 50, 65 mL, inoculum volume percentage: 10, 30 % and agitation speed: 25, 60 rpm) cultures were study in T-flask and spinner flask, respectively. The optimal liquid column height was 5 mm for static culture. The maximum viable cell concentration in spinner flask cultures was reached with 50 mL working volume and the inoculum volume percentage was not significant in the range under study (10-30 %) at 25 rpm agitation. Agitation speed at 60 rpm did not change the main kinetic parameters with respect to those observed for 25 rpm. These results allowed for a schedule to produce more than 4 9 10 9 BHK-21 cells from 4 9 10 6 cells in 13 day with 1,051 mL culture medium.

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Process intensification strategies toward cell culture‐based high‐yield production of a fusogenic oncolytic virus

Jaén

Dorn

Neumeyer

et al. 2023

Biotech & Bioengineering

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We present a proof‐of‐concept study for production of a recombinant vesicular stomatitis virus (rVSV)‐based fusogenic oncolytic virus (OV), rVSV‐Newcastle disease virus (NDV), at high cell densities (HCD). Based on comprehensive experiments in 1 L stirred tank reactors (STRs) in batch mode, first optimization studies at HCD were carried out in semi‐perfusion in small‐scale cultivations using shake flasks. Further, a perfusion process was established using an acoustic settler for cell retention. Growth, production yields, and process‐related impurities were evaluated for three candidate cell lines (AGE1.CR, BHK‐21, HEK293SF)infected at densities ranging from 15 to 30 × 106 cells/mL. The acoustic settler allowed continuous harvesting of rVSV‐NDV with high cell retention efficiencies (above 97%) and infectious virus titers (up to 2.4 × 109 TCID50/mL), more than 4–100 times higher than for optimized batch processes. No decrease in cell‐specific virus yield (CSVY) was observed at HCD, regardless of the cell substrate. Taking into account the accumulated number of virions both from the harvest and bioreactor, a 15–30 fold increased volumetric virus productivity for AGE1.CR and HEK293SF was obtained compared to batch processes performed at the same scale. In contrast to all previous findings, formation of syncytia was observed at HCD for the suspension cells BHK 21 and HEK293SF. Oncolytic potency was not affected compared to production in batch mode. Overall, our study describes promising options for the establishment of perfusion processes for efficient large‐scale manufacturing of fusogenic rVSV‐NDV at HCD for all three candidate cell lines.

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Viral Vaccine Production in Cell Culture

Cited by 22 publications

References 481 publications

Use of uniform designs in combination with neural networks for viral infection process development

Use of uniform designs in combination with neural networks for viral infection process development

Approach toward an efficient inoculum preparation stage for suspension BHK-21 cell culture

Process intensification strategies toward cell culture‐based high‐yield production of a fusogenic oncolytic virus

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